Materiały źródłowe

• #1 Physiology, Cholesterol – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470561/

  Cholesterol is a lipophilic molecule that is essential for human life. […] While cholesterol is central to many healthy cell functions, it also can harm the body if it is allowed to reach abnormal blood concentrations. Interestingly, when LDL-cholesterol levels are too high, the condition referred to as hypercholesterolemia, the risk for premature atherosclerotic cardiovascular diseases (ASCVD) increases. […] Hypercholesterolemia (high LDL-cholesterol) is one of the major risk factors contributing to the formation of atherosclerotic plaques. […] A major contributor to the increased risk of atherosclerotic lesion formation is high levels of low-density lipoprotein (LDL) in the blood. […] The process through which atherosclerotic plaques develop begins with endothelial damage. Endothelial damage leads to the dysfunction of endothelial cells, increasing the number of LDL particles that can permeate through the vascular wall.

• #1 High cholesterol – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/symptoms-causes/syc-20350800

  Cholesterol is a waxy substance found in the blood. The body needs cholesterol to build healthy cells. But high levels of cholesterol can raise the risk of heart disease. […] With high cholesterol, fats and other substances can build up in blood vessels called arteries. This buildup is called plaque. As more plaque forms over time, the arteries can become narrowed or clogged. That makes it hard for enough blood to flow through the arteries. Sometimes a piece of plaque can break loose and form a blood clot. The clot may cause a heart attack or stroke. […] Cholesterol travels through the blood, attached to proteins. This mix of proteins and cholesterol is called a lipoprotein. There are various types of cholesterol. The types are based on what the lipoprotein carries. […] Low-density lipoprotein (LDL) cholesterol. This is known as the „bad” cholesterol. LDL carries cholesterol particles throughout the body. „Bad” cholesterol builds up in the walls of arteries. This makes the arteries hard and narrow.

• #1 Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01125-5

  Disturbed cholesterol homeostasis plays critical roles in the development of multiple diseases, such as cardiovascular diseases (CVD), neurodegenerative diseases and cancers, particularly the CVD in which the accumulation of lipids (mainly the cholesteryl esters) within macrophage/foam cells underneath the endothelial layer drives the formation of atherosclerotic lesions eventually. […] Maintaining cholesterol homeostasis is determined by cholesterol biosynthesis, uptake, efflux, transport, storage, utilization, and/or excretion. All the processes should be precisely controlled by the multiple regulatory pathways. […] Mounting evidence has established the intricate link between cholesterol levels and atherosclerotic cardiovascular disease (ASCVD). […] Accumulation of cholesterol in atherosclerotic plaques may lead to formation of cholesterol crystals, a hallmark of advanced atherosclerotic plaques.

• #1 How it’s made: Cholesterol production in your body – Harvard Health

  https://www.health.harvard.edu/heart-health/how-its-made-cholesterol-production-in-your-body

  Only about 20% of the cholesterol in your bloodstream comes from the food you eat. Your body makes the rest. […] Excess cholesterol in the bloodstream is a key contributor to artery-clogging plaque, which can accumulate and set the stage for a heart attack. […] Cholesterol also is needed to make vitamin D, hormones (including testosterone and estrogen), and fat-dissolving bile acids. […] In fact, cholesterol production is so important that your liver and intestines make about 80% of the cholesterol you need to stay healthy. […] Since cholesterol is a fat, it can’t travel alone in the bloodstream. […] To get around this problem, the body packages cholesterol and other lipids into minuscule protein-covered particles that mix easily with blood. […] Cholesterol and other lipids circulate in the bloodstream in several different forms.

• #1 Cholesterol – Wikipedia

  https://en.wikipedia.org/wiki/Cholesterol

  Cholesterol is biosynthesized by all animal cells and is an essential structural and signaling component of animal cell membranes. In vertebrates, hepatic cells typically produce the greatest amounts. In the brain, astrocytes produce cholesterol and transport it to neurons. […] Elevated levels of cholesterol in the blood, especially when bound to low-density lipoprotein (LDL, often referred to as „bad cholesterol”), may increase the risk of cardiovascular disease. […] De novo synthesis, both in astrocytes and hepatocytes, occurs by a complex 37-step process. This begins with the mevalonate or HMG-CoA reductase pathway, the target of statin drugs, which encompasses the first 18 steps. This is followed by 19 additional steps to convert the resulting lanosterol into cholesterol. […] Cholesterol regulates the biological process of substrate presentation and the enzymes that use substrate presentation as a mechanism of their activation.

• #1 Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01125-5

  Cholesterol can interact with unmatured SREBP on the ER. […] Thus, when the cellular cholesterol level is reduced, the mature SREBP is increased and consequently to activate HMGCR expression. […] Reciprocally, increased cellular cholesterol level inhibits HMGCR expression. […] The seminal work by Goldstein and Brown strongly supports the importance of lipid hypothesis in onset of cardiovascular diseases (CVD). […] Based on the evidence from epidemiological studies and randomized clinical trials, a cholesterol hypothesis was suggested which indicates the high circulating cholesterol level as a major risk factor for ASCVD while cholesterol-lowering strategies can reduce ASCVD risk. […] Statins deprive hepatocytes of endogenous synthesis as a source of cholesterol, which can alleviate the feedback inhibition of LDLR, and thus the increased LDLR expression will further reduce plasma LDL-C levels.

• #1 Structural Basis and Functional Mechanism of Lipoprotein in Cholesterol Transport | IntechOpen

  https://www.intechopen.com/chapters/60397

  Lipoprotein transports lipids in circulation and is primary driver/modulator of atherosclerosis. Highly dynamics of lipoprotein conformations are crucial to lipid transport along the cholesterol transport pathway, where high-density lipoprotein (HDL), low-density lipoprotein (LDL) and cholesteryl ester transfer protein (CETP) are major players in lipid digestion transport and the plasma cholesterol metabolism. […] Hence, the lipoprotein-mediated cholesterol metabolism (cholesterol transport) has aroused great attention and showed the benefit for the in-depth understanding of CVDs, as well as the prevention and treatment of CVDs. […] The last two might be the significant sections of cholesterol transport and metabolism: (1) LDL could transfer lipids into the blood vessel walls, and contribute to the atherosclerosis, which causally be associated with CVD and all-cause mortality; (2) HDL could remove the lipids and carry them back to the liver, being regarded as good one.

• #1 Physiology, Cholesterol – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470561/

  Genetic defects that lead to increased LDL levels in the blood include genes that regulate LDL receptors in the liver. […] Endocytosis of LDL is the primary way that the body decreases cholesterol levels, so it follows that a decrease in LDL receptor function would also increase LDL concentrations in the blood. […] Hypercholesterolemia is often treated medically with lifestyle modification and medications. The goal of lifestyle changes is typically for the patient to increase physical activity, lose weight, and follow a heart-healthy diet.

• #1 Hypercholesterolemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459188/

  High cholesterol can be defined as a LDL-cholesterol greater than 190 mg/dL, greater than 160 mg/dL with one major risk factor, or greater than 130 mg/dL with two cardiovascular risk factors. […] There are genetic and acquired causes of hypercholesterolemia. The classical genetic disorder is familial hypercholesterolemia due to mutations in the LDL-receptor gene resulting in LDL-C greater than 190 mg/dl in heterozygotes and greater than 450 mg/dl in homozygotes. This defect in the LDL receptor accounts for at least 85% of familial hypercholesterolemia. Familial hypercholesterolemia is caused by loss-of-function mutations in the gene encoding the LDL receptor. The reduction in LDL receptor activity in the liver results in a reduced rate of clearance of LDL from the circulation. The plasma level of LDL increases to a level such that the rate of LDL production equals the rate of LDL clearance by residual LDL receptors as well as non-LDL receptor mechanisms.

• #1 Physiology, Cholesterol – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470561/

  As more lipid accumulates within the vessel wall, smooth muscle cells begin to migrate into the lesion. Ultimately, these smooth muscle cells encapsulate the newly formed plaque forming the fibrous plaque, the protector of the lesion, preventing the lipid core from being exposed to the lumen of the vessel. […] Hypercholesterolemia refers to the condition in which a patient has elevated blood concentrations of LDL-cholesterol. High LDL is of particular clinical importance, but it should be noted that hypercholesterolemia can also include very-low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL), i.e., non-HDL-cholesterol. […] Several factors can lead to increased LDL levels. Some of these factors include genetics, diet, stress, sedentary lifestyle, medications, and other disorders such as nephrotic syndrome and hypothyroidism.

• #1 Cholesterol | eClinpath

  https://eclinpath.com/chemistry/energy-metabolism/cholesterol/

  High total cholesterol is usually due to increased numbers of cholesterol-rich lipoproteins, i.e. HDL and LDL. […] The exact mechanism is unknown but the following have been postulated: Increased VLDL production due to hypoalbuminemia or decreased oncotic pressure, defective LDL/HDL processing, increased production of cholesterol-rich lipoproteins or defective conversion of cholesterol to bile acids. […] In dogs, hypothyroidism is associated with mild to marked elevations in cholesterol, due to increased LDL and HDL. […] Cholestasis can result in production of a cholesterol-rich lipoprotein called lipoprotein-X, but the reasons why and how this lipoprotein is formed is unclear. […] Hypercholesterolemia is due to increased LDL, thought to be due to peripheral insulin resistance and down-regulation of LDL receptors in the liver. […] Cholesterol is normally excreted in bile. […] Inflammatory cytokines have been shown to decrease hepatic synthesis and secretion of lipoproteins or alter their lipid composition in humans.

• #1

  https://journals.lww.com/co-lipidology/fulltext/2016/10000/the_central_role_of_arterial_retention_of.6.aspx

  Today, it is no longer a hypothesis, but an established fact, that increased plasma concentrations of cholesterol-rich apolipoprotein-B (apoB)-containing lipoproteins are causatively linked to atherosclerotic cardiovascular disease (ASCVD) and that lowering plasma LDL concentrations reduces cardiovascular events in humans. […] Here, we review evidence behind this assertion, with an emphasis on recent studies supporting the response-to-retention model namely, that the key initiating event in atherogenesis is the retention, or trapping, of cholesterol-rich apoB-containing lipoproteins within the arterial wall. […] LDL and other cholesterol-rich, apoB-containing lipoproteins, once they become retained and modified within the arterial wall, cause atherosclerosis. This simple, robust pathophysiologic understanding may finally allow us to eradicate ASCVD, the leading killer in the world. […] After decades of research, however, there is now a large body of evidence to support the response-to-retention hypothesis namely, that the key initiating event in atherogenesis is the retention, or trapping, of cholesterol-rich apoB-containing lipoproteins within the arterial wall.

• #1 Cholesterol crystals in the pathogenesis of atherosclerosis | Nature Reviews Cardiology

  https://www.nature.com/articles/s41569-024-01100-3

  The presence of cholesterol crystals (CCs) in tissues was first described more than 100 years ago. CCs have a pathogenic role in various cardiovascular diseases, including myocardial infarction, aortic aneurysm and, most prominently, atherosclerosis. […] Although incompletely understood, the formation of CCs probably involves pathways that regulate lipid uptake, intracellular lysosome-mediated lipid metabolism, reverse cholesterol transport and autophagy. […] CCs can be taken up by pattern recognition receptors on various cell types, including macrophages, smooth muscle cells and endothelial cells, and cause various inflammatory responses, including NLRP3 inflammasome activation. […] Cholesterol crystals induce mechanical trauma, inflammation, and neo-vascularization in solid cancers as in atherosclerosis.

• #1 High cholesterol – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/symptoms-causes/syc-20350800

  When a gene change causes high cholesterol, the body has trouble removing LDL cholesterol from the blood. Or the body has trouble breaking down LDL cholesterol in the liver. […] If there’s too much cholesterol in the blood, the cholesterol and other substances may form deposits called plaque. Plaque can cause an artery to become narrowed or blocked. If a plaque ruptures, a blood clot can form. Plaque and blood clots can reduce blood flow through an artery. […] High cholesterol can lead to other health conditions called complications. With high cholesterol, a dangerous amount of plaque can build up on the walls of arteries. This is called atherosclerosis. Over time, the plaque buildup can cause arteries to narrow and block blood flow. Less blood flow through the arteries can cause complications such as:

• #1 Hyperlipidemia (High Cholesterol): Levels, Causes, Symptoms & Diagnosis

  https://my.clevelandclinic.org/health/diseases/21656-hyperlipidemia

  Hyperlipidemia, also known as dyslipidemia or high cholesterol, means you have too many lipids (fats) in your blood. […] Too much cholesterol (200 mg/dL to 239 mg/dL is borderline high and 240 mg/dL is high) isn’t healthy because it can create roadblocks in your artery highways where blood travels around to your body. This damages your organs that don’t receive enough blood from your arteries. […] Bad cholesterol (LDL) is the most dangerous type because it causes hardened cholesterol deposits (plaque) to collect inside of your blood vessels. This makes it harder for your blood to get through, which puts you at risk for a stroke or heart attack. The plaque itself can be irritated or inflamed, which can cause a clot to form around it. This can cause a stroke or heart attack depending on where the blockage is.

• #1 The Effects of Cholesterol on the Body

  https://www.healthline.com/health/cholesterol/effects-on-body

  When plaque builds up in coronary arteries, it can disrupt the flow of oxygen-rich blood to your heart muscle. This may cause chest pain called angina. Angina indicates a temporary disruption of blood flow and can signal that you’re at risk for a heart attack. […] A heart attack typically occurs when a piece of plaque breaks off and forms a clot that blocks the entire artery. This disrupts blood flow to part of the heart, which can lead to a heart attack. […] If this process occurs in the brain, it is called a stroke. There are different types of stroke, and this is one of the causes. […] Cholesterol is an essential component of the human brain. In fact, the brain contains about 20% of the body’s entire supply of cholesterol. This fat is essential for the development and protection of nerve cells, which enable the brain to communicate with the rest of the body.

• #1 Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01125-5

  In the absence of LDLR, LDL-C reaches high level in the circulation, eventually deposits in the artery to drive the formation of atherosclerotic plaques. […] The first demonstration of feedback inhibitory loop by the end product in biosynthetic pathways is that cholesterol inhibits its own synthesis intracellularly. […] The SREBP pathway and the HMGCR degradation pathway serve as two major negative feedback regulatory mechanisms to regulate cholesterol de novo synthesis. […] Inhibition of ACLY can also reduce cholesterol synthesis. […] The cholesterol biosynthesis is an intensely regulated process biologically. […] The process is regulated by a negative feedback mechanism with the downstream products. […] The binding of SREBP triggers transcription of HMGCR to speed up cholesterol biosynthesis. […] The binding of SREBP triggers transcription of LDLR to speed up cholesterol clearance. […] In addition to HMGCR, SREBP also regulates LDLR expression in response to cellular cholesterol levels to fine-tune the cholesterol level in cell membranes constant.

• #1 Cholesterol – Wikipedia

  https://en.wikipedia.org/wiki/Cholesterol

  Cholesterol is also implicated in cell signaling processes, assisting in the formation of lipid rafts in the plasma membrane, which brings receptor proteins in close proximity with high concentrations of second messenger molecules. […] Cholesterol binds to and affects the gating of a number of ion channels such as the nicotinic acetylcholine receptor, GABAA receptor, and the inward-rectifier potassium channel. […] Elevated levels of the lipoprotein fractions, LDL, IDL and VLDL, rather than the total cholesterol level, correlate with the extent and progress of atherosclerosis. […] When this process becomes unregulated, LDL particles without receptors begin to appear in the blood. These LDL particles are oxidized and taken up by macrophages, which become engorged and form foam cells. These foam cells often become trapped in the walls of blood vessels and contribute to atherosclerotic plaque formation.

• #1 Cellular insights into high cholesterol

  https://read.houstonmethodist.org/cellular-insights-into-high-cholesterol

  The landmark study identified a new regulatory mechanism responsible for the increase in white blood cells seen in people with high levels of low density lipoprotein (LDL). […] They identified a new regulatory mechanism responsible for this increase in white blood cells typically seen in people with these high LDL levels, which increase a persons risk for cardiovascular disease, the leading cause of morbidity and mortality in the U.S. and globally. […] The mechanism we identified activates a protein called SREBP2 that in turn leads to the development of more hematopoietic stem cells (HSPCs), which are the precursors to white blood cells and the process by which all mature blood cells are produced. […] These findings provide support for the hypothesis that cholesterol metabolism is a driver of inflammation in cardiovascular disease.

• #1 High-density lipoprotein – Wikipedia

  https://en.wikipedia.org/wiki/High-density_lipoprotein

  People with higher levels of HDL-C tend to have fewer problems with cardiovascular diseases, while those with low HDL-C cholesterol levels (especially less than 40 mg/dL or about 1 mmol/L) have increased rates for heart disease. […] Higher native HDL levels are correlated with lowered risk of cardiovascular disease in healthy people. […] However, a higher blood level of HDL is not necessarily protective against cardiovascular disease and may even be harmful in extremely high quantities, with an increased cardiovascular risk, especially in hypertensive patients. […] Several steps in the metabolism of HDL can participate in the transport of cholesterol from lipid-laden macrophages of atherosclerotic arteries, termed foam cells, to the liver for secretion into the bile. This pathway has been termed reverse cholesterol transport and is considered as the classical protective function of HDL toward atherosclerosis.

• #1 Structural Basis and Functional Mechanism of Lipoprotein in Cholesterol Transport | IntechOpen

  https://www.intechopen.com/chapters/60397

  It is widely accepted that HDL protein particles alleviate atherosclerosis with better cardiovascular health (reverse cholesterol transport, RCT). […] Therefore, the functions of HDL, LDL and CETP play the important roles during the cholesterol transport (lipoprotein particle metabolism), and pharmacological inhibition of CETP is being regarded as a way to prevent CVDs. […] The apo-B48 (apoprotein B48) and apo-B100 (apoprotein B100) located in surface of LDL particles tend to interact with extracellular material, which make LDL particles easy to bind with blood vessel intima. […] The oxidation-LDL can promote lipoproteins aggregation and provoke inflammation by recruiting the circulating monocytes to the site followed invade the vessel wall and differentiate into macrophages, to finally produce atherosclerotic plaque.

• #1 Impact of Dietary Cholesterol on the Pathophysiology of Infectious and Autoimmune Disease

  https://www.mdpi.com/2072-6643/10/6/764

  Cellular cholesterol metabolism, lipid raft formation, and lipoprotein interactions contribute to the regulation of immune-mediated inflammation and response to pathogens. […] Dysregulation of the immune system has been implicated in a broad range of acute and chronic conditions, ranging from increased susceptibility to infection, autoimmunity, and chronic inflammatory diseases, such as asthma, osteoarthritis, cardiovascular disease, non-alcoholic fatty liver disease, and cancer. […] While most extensively evaluated within the context of cardiovascular disease, dietary cholesterol may serve as an important regulator of immune cell activity and inflammation, with implications for risk and treatment of infectious disease and chronic autoimmune disorders. […] Cellular cholesterol depletion has been shown to disrupt raft stability and formation, as well as suppress toll-like receptor 4 (TLR4)- and T cell receptor (TCR)-mediated immune activation and pro-inflammatory signaling, whereas these processes are enhanced by cholesterol loading.

• #1 Cholesterol crystals in the pathogenesis of atherosclerosis | Nature Reviews Cardiology

  https://www.nature.com/articles/s41569-024-01100-3

  The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. […] Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: a novel link between cholesterol metabolism and inflammation. […] Cholesterol crystal formation is a unifying pathogenic mechanism in the development of diabetic retinopathy. […] Cholesterol crystals rupture biological membranes and human plaques during acute cardiovascular events a novel insight into plaque rupture by scanning electron microscopy. […] Cholesterol crystals increase vascular permeability by inactivating SHP2 and disrupting adherens junctions. […] Cholesterol crystal-induced endothelial cell activation is complement-dependent and mediated by TNF.

• #1 Cholesterol Efflux and Reverse Cholesterol Transport | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-319-09665-0_4

  Both alterations of lipid/lipoprotein metabolism and inflammatory events contribute to the formation of the atherosclerotic plaque, characterized by the accumulation of abnormal amounts of cholesterol and macrophages in the artery wall. […] Reverse cholesterol transport (RCT) may counteract the pathogenic events leading to the formation and development of atheroma, by promoting the high-density lipoprotein (HDL)-mediated removal of cholesterol from the artery wall. […] Recent in vivo studies established the inverse relationship between RCT efficiency and atherosclerotic cardiovascular diseases (CVD), thus suggesting that the promotion of this process may represent a novel strategy to reduce atherosclerotic plaque burden and subsequent cardiovascular events. […] Although the inverse association between HDL plasma levels and CVD risk has been postulated for years, recently this concept has been challenged by studies reporting that HDL antiatherogenic functions may be independent of their plasma levels.

• #1 LDL cholesterol – Lipid Tools

  https://www.lipidtools.com/ldl-cholesterol/

  LDL is an atherogenic lipoprotein that unequivocally is a causal factor for atherosclerotic and cardiovascular disease. […] Every 1 mmol/L reduction in LDL cholesterol results in a relative risk reduction in cardiovascular disease of 20%. […] Familial hypercholesterolemia (FH), for example, is an autosomal co-dominant disorder characterized by accumulating high LDL cholesterol levels from birth onwards that put patients at high risk for cardiovascular disease. […] Mendelian randomization studies have also shown that a 1 mmol/L genetically determined lower LDL cholesterol during a median follow-up of 52 years leads to a 54% risk reduction in cardiovascular disease. […] In conclusion, the exposure to LDL cholesterol throughout life determines the risk of cardiovascular disease.

• #1 High cholesterol – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/symptoms-causes/syc-20350800

  If plaques tear or break, a blood clot can form. The clot may block the flow of blood at the site where it broke. Or it may completely break free and block an artery farther away. If blood flow to part of the heart stops, a heart attack happens. A heart attack is an emergency that needs treatment right away. […] The same heart-healthy lifestyle changes that can lower cholesterol also can help prevent high cholesterol.

• #1 Patient education: High cholesterol and lipid treatment options (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/high-cholesterol-and-lipid-treatment-options-beyond-the-basics/print

  Bempedoic acid (brand name: Nexletol) is the newest lipid-lowering agent, and it is approved for lowering LDL cholesterol. […] Bempedoic acid alone or in combination with a statin or ezetimibe (brand name: Nexlizet) lowers LDL cholesterol as well as other atherogenic proteins. […] Statins are one of the best-studied classes of medications and the most commonly used drugs for lowering LDL cholesterol. […] Statins decrease the body’s production of cholesterol and increase removal of cholesterol by the liver, so they reduce LDL cholesterol levels by as much as 25 to 55 percent. […] Statins may also reduce inflammation and may prevent heart attacks and strokes through this mechanism.

• #1 Patient education: High cholesterol and lipid treatment options (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/high-cholesterol-and-lipid-treatment-options-beyond-the-basics

  Some patients have extremely high levels of LDL cholesterol, eg, >190 mg/dL and a family history of others with such high levels. […] These patients often have a genetic factor that leads to a change in how cholesterol is processed in the body, and they have high levels of cholesterol from birth. […] Statins are one of the best-studied classes of medications and the most commonly used drugs for lowering LDL cholesterol. […] Statins decrease the body’s production of cholesterol and increase removal of cholesterol by the liver, so they reduce LDL cholesterol levels by as much as 25 to 55 percent. […] Statins may also reduce inflammation and may prevent heart attacks and strokes through this mechanism. […] Ezetimibe (brand name: Zetia) blocks the body’s ability to actively transport cholesterol from food as well as cholesterol that the body produces internally.

• #1 What is Familial Hypercholesterolemia? | American Heart Association

  https://www.heart.org/en/health-topics/cholesterol/genetic-conditions/familial-hypercholesterolemia-fh

  Familial hypercholesterolemia (FH) is an inherited defect in how the body recycles LDL, or “bad” cholesterol. […] High LDL contributes to plaque buildup, leading to a much higher-than-normal risk of coronary heart disease. If left untreated, people with FH have 20 times the risk of developing heart disease. […] Familial hypercholesterolemia is commonly caused by a mutation in the gene for the LDL cholesterol receptor, which is involved in passing LDL from the blood into cells for use by, or removal from, the body. […] FH remains underdiagnosed and undertreated. But people with FH have an excellent prognosis if the condition is identified early and treated. […] Familial hypercholesterolemia cannot be treated by diet and exercise alone. These lifestyle changes can help, but medications are recommended to reduce LDL cholesterol levels by at least 50%. […] Injectable medications, known as PCSK9 inhibitors, also can lower cholesterol levels. These medications target and block the PCSK9 protein, which frees up more receptors on liver cells to remove LDL cholesterol from the blood.

• #1 Patient education: High cholesterol and lipid treatment options (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/high-cholesterol-and-lipid-treatment-options-beyond-the-basics/print

  A high cholesterol level (also called „hypercholesterolemia”) can significantly increase your risk of developing chest pain, heart attack, and stroke. […] Higher levels of LDL cholesterol are associated with greater risk of heart attack, stroke, need for stenting or coronary bypass surgery, and death. Studies over the past 50 years have shown that lowering LDL cholesterol leads to lower rates of these cardiac events. […] Cholesterol levels (notably LDL cholesterol and triglycerides) can almost always be lowered with a combination of weight loss (achieved with diet and exercise), and medications. […] As your level decreases, so does your risk of developing cardiovascular disease (CVD), including disease of the blood vessels supplying the heart (coronary artery disease), brain (cerebrovascular disease), and limbs (peripheral vascular disease).

• #1 Patient education: High cholesterol and lipid treatment options (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/high-cholesterol-and-lipid-treatment-options-beyond-the-basics/print

  Studies have shown that in people with coronary heart disease, taking medication to significantly lower the level of „bad” cholesterol, called low-density lipoprotein (LDL) cholesterol, is beneficial. […] Many health care providers recommend treating anyone with CVD (including people who have coronary heart disease or have had a stroke) with high-dose statin therapy. […] Studies have found that if the LDL cholesterol is reduced to less than 70 mg/dL and preferably less than 55 mg/dL, the size of the plaques can get smaller. […] People with high triglyceride levels—Triglycerides, like cholesterol, are a type of lipid. High triglycerides (called „hypertriglyceridemia”) are also associated with an increased risk of heart disease. […] For reducing cardiovascular risk, the first step is to reduce the LDL to below the target level and then check the fasting triglyceride level.

• #1 The mechanism of cholesterol action in the pathogenesis of Alzheimer’s disease – Ruđer BoÅ¡ković Institute

  https://www.irb.hr/eng/Divisions/Division-of-Molecular-Medicine/Laboratory-for-Neurodegenerative-Disease-Research/Projects/The-mechanism-of-cholesterol-action-in-the-pathogenesis-of-Alzheimer-s-disease

  Recent studies reveal that cholesterol may play a role in the pathogenesis of Alzheimers disease (AD). […] Treatment with cholesterol-lowering drugs (statins) appears to lower the risk of developing AD. […] Amyloid- (A) production is associated with cholesterol-rich domains (lipid rafts) and cholesterol levels modulate processing of -amyloid precursor protein (APP) and A generation. […] The goal of this project is to elucidate the mechanism(s) of cholesterol-effect on APP metabolism and the genesis of Alzheimers disease. […] We hypothesize that cholesterol modulates APP processing both directly and indirectly. […] We speculate that cholesterol regulation of membrane and protein trafficking along the endocytic pathway leads to amyloidogenic processing of APP. […] Lastly, we hypothesize that cholesterol metabolism is altered in patients with Alzheimers disease and that this effect is related to apoE genotype. […] Our findings may suggest that maintaining normal cholesterol homeostasis could protect and/or delay progression of Alzheimers disease.

• #1 Polygenic Hypercholesterolemia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/121424-overview

  Polygenic hypercholesterolemia is the most common cause of elevated serum cholesterol concentrations. Low-density lipoprotein cholesterol (LDL-C) elevations are moderate (140-300 mg/dL) with serum triglyceride concentrations within the reference range. […] Polygenic hypercholesterolemia is caused by a susceptible genotype aggravated by one or more factors, including atherogenic diet (excessive intake of saturated fat, trans fat, and, to a lesser extent, cholesterol), obesity, and sedentary lifestyle. The involved genes have yet to be discovered. Polygenic hypercholesterolemia is associated with an increased risk for coronary heart disease (CHD), as displayed in the image below. […] Elevated LDL-C concentrations may be the consequence of elevated LDL production or decreased LDL hepatic uptake. The liver is responsible for high LDL-C levels, as follows: Overproduction of VLDL particles, which are converted to VLDL remnants or IDL particles by lipoprotein lipase and then to LDL particles by hepatic lipase (which occurs with diet high in triglycerides), or inefficient uptake by the LDL receptors (Diets high in saturated fat, trans fat, and cholesterol cause a reduction in LDL receptors in the liver, thus retarding LDL catabolism.)

• #1 What is the role of lipids in atherosclerosis and how low should we decrease lipid levels?

  https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-18/what-is-the-role-of-lipids-in-atherosclerosis-and-how-low-should-we-decrease-lip

  Retention of apolipoprotein-B-containing lipoproteins within the arterial wall is the key initiating event in the pathobiology of atherosclerosis. […] Compelling evidence from preclinical investigations, Mendelian randomisation studies, epidemiologic observations, and randomised trials of lipid-modifying medications supports the key causal role of atherogenic lipoproteins, particularly low-density lipoprotein (LDL), in the pathogenesis of ASCVD. […] Importantly, dyslipidaemia is a modifiable risk factor, and pharmacologic LDL-cholesterol (LDL-C) lowering has been shown to halt the progression of atherosclerosis and improve clinical outcomes in the context of primary as well as secondary prevention. […] The totality of currently available evidence indicates that the greater the absolute reduction in plasma LDL-C levels, the larger the reduction of ASCVD risk, without offsetting safety issues arising from intensive lipid-lowering strategies.

• #2 Hypercholesterolemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459188/

  High cholesterol can be defined as a LDL-cholesterol greater than 190 mg/dL, greater than 160 mg/dL with one major risk factor, or greater than 130 mg/dL with two cardiovascular risk factors. […] There are genetic and acquired causes of hypercholesterolemia. The classical genetic disorder is familial hypercholesterolemia due to mutations in the LDL-receptor gene resulting in LDL-C greater than 190 mg/dl in heterozygotes and greater than 450 mg/dl in homozygotes. This defect in the LDL receptor accounts for at least 85% of familial hypercholesterolemia. Familial hypercholesterolemia is caused by loss-of-function mutations in the gene encoding the LDL receptor. The reduction in LDL receptor activity in the liver results in a reduced rate of clearance of LDL from the circulation. The plasma level of LDL increases to a level such that the rate of LDL production equals the rate of LDL clearance by residual LDL receptors as well as non-LDL receptor mechanisms.

• #2 How it’s made: Cholesterol production in your body – Harvard Health

  https://www.health.harvard.edu/heart-health/how-its-made-cholesterol-production-in-your-body

  Only about 20% of the cholesterol in your bloodstream comes from the food you eat. Your body makes the rest. […] Excess cholesterol in the bloodstream is a key contributor to artery-clogging plaque, which can accumulate and set the stage for a heart attack. […] Cholesterol also is needed to make vitamin D, hormones (including testosterone and estrogen), and fat-dissolving bile acids. […] In fact, cholesterol production is so important that your liver and intestines make about 80% of the cholesterol you need to stay healthy. […] Since cholesterol is a fat, it can’t travel alone in the bloodstream. […] To get around this problem, the body packages cholesterol and other lipids into minuscule protein-covered particles that mix easily with blood. […] Cholesterol and other lipids circulate in the bloodstream in several different forms.

• #2 Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01125-5

  In the absence of LDLR, LDL-C reaches high level in the circulation, eventually deposits in the artery to drive the formation of atherosclerotic plaques. […] The first demonstration of feedback inhibitory loop by the end product in biosynthetic pathways is that cholesterol inhibits its own synthesis intracellularly. […] The SREBP pathway and the HMGCR degradation pathway serve as two major negative feedback regulatory mechanisms to regulate cholesterol de novo synthesis. […] Inhibition of ACLY can also reduce cholesterol synthesis. […] The cholesterol biosynthesis is an intensely regulated process biologically. […] The process is regulated by a negative feedback mechanism with the downstream products. […] The binding of SREBP triggers transcription of HMGCR to speed up cholesterol biosynthesis. […] The binding of SREBP triggers transcription of LDLR to speed up cholesterol clearance. […] In addition to HMGCR, SREBP also regulates LDLR expression in response to cellular cholesterol levels to fine-tune the cholesterol level in cell membranes constant.

• #2 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Cholesterol-Physiology.aspx

  High levels of cholesterol in blood circulation, depending on how it is transported within lipoproteins, are strongly associated with progression of atherosclerosis. […] The synthesis of cholesterol begins with a molecule of acetyl CoA and one molecule of acetoacetyl-CoA, which are dehydrated to form 3-hydroxy-3-methylglutaryl CoA (HMG-CoA). This molecule is then reduced to mevalonate by the enzyme HMG-CoA reductase. This step is an irreversible step in cholesterol synthesis. This step is blocked by cholesterol lowering drugs like Statins. […] Biosynthesis of cholesterol is directly regulated by the cholesterol levels present. When too much intake of cholesterol from food is detected there is a reduction in endogenous cholesterol synthesis. The main regulatory mechanism is the sensing of intracellular cholesterol in the endoplasmic reticulum by the protein SREBP (sterol regulatory element-binding protein 1 and 2).

• #2 How it’s made: Cholesterol production in your body – Harvard Health

  https://www.health.harvard.edu/heart-health/how-its-made-cholesterol-production-in-your-body

  Low-density lipoprotein (LDL) particles are even richer in pure cholesterol, since most of the triglycerides they carried are gone. LDL is known as „bad” cholesterol because it delivers cholesterol to tissues and is strongly associated with the buildup of artery-clogging plaque. […] High-density lipoprotein (HDL) particles are called „good” cholesterol because some of them remove cholesterol from circulation and from artery walls and return it to the liver for excretion.

• #2 Hypercholesterolemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459188/

  It is believed that the elevated LDL particles permeate the vascular intima and get trapped by proteoglycans in the intima. In the intima, LDL is oxidatively modified and promote inflammation and fatty streak formation. Atherogenesis evolves through a fibrous plaque to the mature lesion with plaque rupture culminating in a CV event. […] In familial hypercholesterolemia, there is either a problem with the LDL receptor or it is missing. Without the receptor, uptake of cholesterol into the liver is not possible. The liver usually processes two-thirds of the circulating LDL. Hundreds of mutations of the LDL receptor have been identified, which express themselves as hypercholesterolemia.

• #2 High cholesterol – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/symptoms-causes/syc-20350800

  When a gene change causes high cholesterol, the body has trouble removing LDL cholesterol from the blood. Or the body has trouble breaking down LDL cholesterol in the liver. […] If there’s too much cholesterol in the blood, the cholesterol and other substances may form deposits called plaque. Plaque can cause an artery to become narrowed or blocked. If a plaque ruptures, a blood clot can form. Plaque and blood clots can reduce blood flow through an artery. […] High cholesterol can lead to other health conditions called complications. With high cholesterol, a dangerous amount of plaque can build up on the walls of arteries. This is called atherosclerosis. Over time, the plaque buildup can cause arteries to narrow and block blood flow. Less blood flow through the arteries can cause complications such as:

• #2 Polygenic Hypercholesterolemia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/121424-overview

  Polygenic hypercholesterolemia is the most common cause of elevated serum cholesterol concentrations. Low-density lipoprotein cholesterol (LDL-C) elevations are moderate (140-300 mg/dL) with serum triglyceride concentrations within the reference range. […] Polygenic hypercholesterolemia is caused by a susceptible genotype aggravated by one or more factors, including atherogenic diet (excessive intake of saturated fat, trans fat, and, to a lesser extent, cholesterol), obesity, and sedentary lifestyle. The involved genes have yet to be discovered. Polygenic hypercholesterolemia is associated with an increased risk for coronary heart disease (CHD), as displayed in the image below. […] Elevated LDL-C concentrations may be the consequence of elevated LDL production or decreased LDL hepatic uptake. The liver is responsible for high LDL-C levels, as follows: Overproduction of VLDL particles, which are converted to VLDL remnants or IDL particles by lipoprotein lipase and then to LDL particles by hepatic lipase (which occurs with diet high in triglycerides), or inefficient uptake by the LDL receptors (Diets high in saturated fat, trans fat, and cholesterol cause a reduction in LDL receptors in the liver, thus retarding LDL catabolism.)

• #2 Cholesterol | MedlinePlus

  https://medlineplus.gov/cholesterol.html

  Genetics may also cause people to have high cholesterol. For example, familial hypercholesterolemia (FH) is an inherited condition that causes very high levels of cholesterol in the blood. Other medical conditions and certain medicines may also raise LDL cholesterol levels or lower HDL cholesterol levels. […] Undiagnosed or untreated high blood cholesterol can lead to serious health problems: If you have large deposits of plaque in your arteries, an area of plaque can rupture (break open). This can cause a blood clot to form on the surface of the plaque. If the clot becomes large enough, it can mostly or completely block blood flow in a coronary artery. […] You can lower your cholesterol through heart-healthy lifestyle changes. They include a heart-healthy eating plan, weight management, and regular physical activity.

• #2

  https://journals.lww.com/co-lipidology/fulltext/2016/10000/the_central_role_of_arterial_retention_of.6.aspx

  Today, it is no longer a hypothesis, but an established fact, that increased plasma concentrations of cholesterol-rich apolipoprotein-B (apoB)-containing lipoproteins are causatively linked to atherosclerotic cardiovascular disease (ASCVD) and that lowering plasma LDL concentrations reduces cardiovascular events in humans. […] Here, we review evidence behind this assertion, with an emphasis on recent studies supporting the response-to-retention model namely, that the key initiating event in atherogenesis is the retention, or trapping, of cholesterol-rich apoB-containing lipoproteins within the arterial wall. […] LDL and other cholesterol-rich, apoB-containing lipoproteins, once they become retained and modified within the arterial wall, cause atherosclerosis. This simple, robust pathophysiologic understanding may finally allow us to eradicate ASCVD, the leading killer in the world. […] After decades of research, however, there is now a large body of evidence to support the response-to-retention hypothesis namely, that the key initiating event in atherogenesis is the retention, or trapping, of cholesterol-rich apoB-containing lipoproteins within the arterial wall.

• #2 What is the role of lipids in atherosclerosis and how low should we decrease lipid levels?

  https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-18/what-is-the-role-of-lipids-in-atherosclerosis-and-how-low-should-we-decrease-lip

  Retention of apolipoprotein-B-containing lipoproteins within the arterial wall is the key initiating event in the pathobiology of atherosclerosis. […] Compelling evidence from preclinical investigations, Mendelian randomisation studies, epidemiologic observations, and randomised trials of lipid-modifying medications supports the key causal role of atherogenic lipoproteins, particularly low-density lipoprotein (LDL), in the pathogenesis of ASCVD. […] Importantly, dyslipidaemia is a modifiable risk factor, and pharmacologic LDL-cholesterol (LDL-C) lowering has been shown to halt the progression of atherosclerosis and improve clinical outcomes in the context of primary as well as secondary prevention. […] The totality of currently available evidence indicates that the greater the absolute reduction in plasma LDL-C levels, the larger the reduction of ASCVD risk, without offsetting safety issues arising from intensive lipid-lowering strategies.

• #2 Physiology, Cholesterol – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470561/

  As more lipid accumulates within the vessel wall, smooth muscle cells begin to migrate into the lesion. Ultimately, these smooth muscle cells encapsulate the newly formed plaque forming the fibrous plaque, the protector of the lesion, preventing the lipid core from being exposed to the lumen of the vessel. […] Hypercholesterolemia refers to the condition in which a patient has elevated blood concentrations of LDL-cholesterol. High LDL is of particular clinical importance, but it should be noted that hypercholesterolemia can also include very-low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL), i.e., non-HDL-cholesterol. […] Several factors can lead to increased LDL levels. Some of these factors include genetics, diet, stress, sedentary lifestyle, medications, and other disorders such as nephrotic syndrome and hypothyroidism.

• #2 Cholesterol crystals in the pathogenesis of atherosclerosis | Nature Reviews Cardiology

  https://www.nature.com/articles/s41569-024-01100-3

  The presence of cholesterol crystals (CCs) in tissues was first described more than 100 years ago. CCs have a pathogenic role in various cardiovascular diseases, including myocardial infarction, aortic aneurysm and, most prominently, atherosclerosis. […] Although incompletely understood, the formation of CCs probably involves pathways that regulate lipid uptake, intracellular lysosome-mediated lipid metabolism, reverse cholesterol transport and autophagy. […] CCs can be taken up by pattern recognition receptors on various cell types, including macrophages, smooth muscle cells and endothelial cells, and cause various inflammatory responses, including NLRP3 inflammasome activation. […] Cholesterol crystals induce mechanical trauma, inflammation, and neo-vascularization in solid cancers as in atherosclerosis.

• #2 Cholesterol crystals in the pathogenesis of atherosclerosis | Nature Reviews Cardiology

  https://www.nature.com/articles/s41569-024-01100-3

  The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. […] Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: a novel link between cholesterol metabolism and inflammation. […] Cholesterol crystal formation is a unifying pathogenic mechanism in the development of diabetic retinopathy. […] Cholesterol crystals rupture biological membranes and human plaques during acute cardiovascular events a novel insight into plaque rupture by scanning electron microscopy. […] Cholesterol crystals increase vascular permeability by inactivating SHP2 and disrupting adherens junctions. […] Cholesterol crystal-induced endothelial cell activation is complement-dependent and mediated by TNF.

• #2 High cholesterol – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/symptoms-causes/syc-20350800

  If plaques tear or break, a blood clot can form. The clot may block the flow of blood at the site where it broke. Or it may completely break free and block an artery farther away. If blood flow to part of the heart stops, a heart attack happens. A heart attack is an emergency that needs treatment right away. […] The same heart-healthy lifestyle changes that can lower cholesterol also can help prevent high cholesterol.

• #2 Hyperlipidemia (High Cholesterol): Levels, Causes, Symptoms & Diagnosis

  https://my.clevelandclinic.org/health/diseases/21656-hyperlipidemia

  Hyperlipidemia can be very serious if it’s not managed. As long as high cholesterol is untreated, you’re letting plaque accumulate inside of your blood vessels. This can lead to a heart attack or stroke because your blood has a hard time getting through your blood vessels. This deprives your brain and heart of the nutrients and oxygen they need to function. […] Hyperlipidemia (high cholesterol) that’s not treated can allow plaque to collect inside of your body’s blood vessels (atherosclerosis). […] Although high cholesterol puts you at risk for heart attacks and stroke, you can protect yourself by living a healthier lifestyle and taking medicine if needed.

• #2 The Effects of Cholesterol on the Body

  https://www.healthline.com/health/cholesterol/effects-on-body

  While you need some cholesterol for your brain to function optimally, too much of it can be damaging. Excess cholesterol in the arteries can lead to stroke a disruption in blood flow that can damage parts of the brain. […] High LDL cholesterol has also been associated with the risk of vascular dementia, a type of dementia that affects memory, thinking, and behavior. […] Yet having too much LDL cholesterol can, over time, damage your arteries, contribute to heart disease, and increase your risk for stroke.

• #2 Impact of Dietary Cholesterol on the Pathophysiology of Infectious and Autoimmune Disease

  https://www.mdpi.com/2072-6643/10/6/764

  Cellular cholesterol metabolism, lipid raft formation, and lipoprotein interactions contribute to the regulation of immune-mediated inflammation and response to pathogens. […] Dysregulation of the immune system has been implicated in a broad range of acute and chronic conditions, ranging from increased susceptibility to infection, autoimmunity, and chronic inflammatory diseases, such as asthma, osteoarthritis, cardiovascular disease, non-alcoholic fatty liver disease, and cancer. […] While most extensively evaluated within the context of cardiovascular disease, dietary cholesterol may serve as an important regulator of immune cell activity and inflammation, with implications for risk and treatment of infectious disease and chronic autoimmune disorders. […] Cellular cholesterol depletion has been shown to disrupt raft stability and formation, as well as suppress toll-like receptor 4 (TLR4)- and T cell receptor (TCR)-mediated immune activation and pro-inflammatory signaling, whereas these processes are enhanced by cholesterol loading.

• #2 New insights into the mechanism of low high-density lipoprotein cholesterol in obesity | Lipids in Health and Disease | Full Text

  https://lipidworld.biomedcentral.com/articles/10.1186/1476-511X-10-176

  As an antiatherogenic adipokine, APN has critical influence on HDL metabolism. […] The upregulation of SREBP-1c would activate its downstream genes, such as fatty acid synthetase (FAS) and acetyl-CoA carboxylase (ACC) and accelerate TG and VLDL synthesis. […] Thus, elevated plasma TG level and reduced HDL-C level would be manifested simultaneously in obese individuals. […] These new findings provide new clues to the understanding of the potential mechanism of low HDL-C in obesity and potential targets for preventing and treating HDL-C reduction.

• #2 Cholesterol Efflux and Reverse Cholesterol Transport | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-319-09665-0_4

  Both alterations of lipid/lipoprotein metabolism and inflammatory events contribute to the formation of the atherosclerotic plaque, characterized by the accumulation of abnormal amounts of cholesterol and macrophages in the artery wall. […] Reverse cholesterol transport (RCT) may counteract the pathogenic events leading to the formation and development of atheroma, by promoting the high-density lipoprotein (HDL)-mediated removal of cholesterol from the artery wall. […] Recent in vivo studies established the inverse relationship between RCT efficiency and atherosclerotic cardiovascular diseases (CVD), thus suggesting that the promotion of this process may represent a novel strategy to reduce atherosclerotic plaque burden and subsequent cardiovascular events. […] Although the inverse association between HDL plasma levels and CVD risk has been postulated for years, recently this concept has been challenged by studies reporting that HDL antiatherogenic functions may be independent of their plasma levels.

• #2 Structural Basis and Functional Mechanism of Lipoprotein in Cholesterol Transport | IntechOpen

  https://www.intechopen.com/chapters/60397

  CETP acts as a medium between lipoproteins for elevating plasma LDL-C (or VLDL-C) level and lowering HDL-C level. […] CETP shows a high binding affinity for nascent HDL and other lipoproteins to cover the lipoproteins surfaces owing to its proper curvature radius. […] In this model, both CETP terminals finish penetrating surface sites on lipoproteins, N-terminal to HDL and C-terminal to LDL (or VLDL). Then neutral lipids, including cholesterol esters and triglycerides, transfer through the hydrophobic tunnel at the core of the CETP.

• #2 Impact of Dietary Cholesterol on the Pathophysiology of Infectious and Autoimmune Disease

  https://www.mdpi.com/2072-6643/10/6/764

  In addition to regulating cellular signaling and inflammatory potential, lipid rafts serve as a point of pathogen association and colonization. […] Cholesterol is thought to mediate host cell infection by these Gram-negative bacterial strains through recognition and binding of the virulence factor cytolethal distending toxin (CDT), and mediating subsequent translocation of active toxin subunits. […] In addition to infectious disease pathways, cholesterol metabolism appears to play an important role in autoimmune disease. […] In patients with systemic lupus erythematous (SLE), T lymphocytes exhibit greater degrees of lipid raft formation and altered raft composition, leading to increased TCR-mediated signaling and inflammation. […] Dysregulation of lipid pathways may additionally contribute to inappropriate leukocyte activation and inflammation in autoimmune disorders. […] Taken together, research shows that lipid rafts and lipoprotein interactions are not only essential in the pathogenesis of infectious disease, but also in the compensatory immune response to ameliorate infection.

• #2 Study Highlights Mechanism Connecting Diabetes, Elevated Cholesterol

  https://www.ajmc.com/view/study-highlights-mechanism-connecting-diabetes-elevated-cholesterol

  The connection between diabetes and cardiovascular disease is well-established. According to the American Heart Association, diabetes tends to lower high-density lipoprotein or good cholesterol, while increasing low-density lipoprotein (LDL) or bad cholesterol, thus increasing the likelihood of heart disease or stroke. […] Researchers from Helmholtz Zentrum Munchen, Technisch Universitat Munchen, known as TUM, conducted a series of experiments to uncover the mechanism that can cause hypercholesterolemia and increased lipid deposits in the arteries. […] The scientists demonstrated how TNF- signaling, via ROS, blocked GAbp. It turns out the liver protein is a regulator of another protein, AMPK, which controls levels of cholesterol. […] The work in this study shows the key role of GAbp as a regulator between inflammation, cholesterol homeostasis, and atherosclerosis, she said. Without the protective effect of GAbp, Niopek said, this leads to hypercholesterolemia, and increased lipid deposition in the arteries. […] Thus, inflammation in diabetes sets off a chain of events that elevates cholesterol causes atherosclerosis to develop over time, the researchers found.

• #2 The Role of Cholesterol in Chronic Lymphocytic Leukemia Development and Pathogenesis

  https://www.mdpi.com/2218-1989/13/7/799

  Cholesterol has many critical functions in cells. It is a key component of membranes and cell-signalling processes, and it functions as a chemical precursor in several biochemical pathways, such as Vitamin D and steroid synthesis. Cholesterol has also been implicated in the development and progression of various cancers, in which it is thought to promote cell proliferation, migration, and invasion. Chronic lymphocytic leukemia (CLL) is an example of a lipid-avid cancer that relies on lipid metabolism, rather than glycolysis, to fuel cell proliferation. […] Studies suggest that rates of dyslipidemia are higher among CLL patients than age-matched healthy controls. One study showed that CLL patients suffer from hypercholesterolemia, observing elevated LDL levels in 75% of CLL patients. […] Hypercholesteremia may be due to an increase in the hepatic secretion of cholesterol into the blood stream; this may potentially fuel the rapid proliferation of leukemic cells in patients with a poor prognosis.

• #2 Cholesterol Efflux and Reverse Cholesterol Transport | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-319-09665-0_4

  Therefore, assessment of HDL function, evaluated as the capacity to promote cell cholesterol efflux may offer a better prediction of CVD than HDL levels alone. […] Consistent with this idea, it has been recently demonstrated that the evaluation of serum cholesterol efflux capacity (CEC) is a predictor of atherosclerosis extent in humans. […] The efflux process involves cholesterol localized on the plasma membrane that in turn may derive from intracellular sites, such as the late endosomal/lysosomal compartment and from the Golgi apparatus. […] Mechanisms accounting for cholesterol efflux include passive diffusion processes as well as active pathways mediated by ABCA1, ABCG1, and scavenger receptor class B type I (SR-BI). […] The nature of this process is a matter of debate: whereas this mechanism appears to be a relevant contributor of lipid removal in foam cell macrophages, the involvement of a still unknown transporter is not completely ruled out.

• #2 The Effects of Cholesterol on the Body

  https://www.healthline.com/health/cholesterol/effects-on-body

  When plaque builds up in coronary arteries, it can disrupt the flow of oxygen-rich blood to your heart muscle. This may cause chest pain called angina. Angina indicates a temporary disruption of blood flow and can signal that you’re at risk for a heart attack. […] A heart attack typically occurs when a piece of plaque breaks off and forms a clot that blocks the entire artery. This disrupts blood flow to part of the heart, which can lead to a heart attack. […] If this process occurs in the brain, it is called a stroke. There are different types of stroke, and this is one of the causes. […] Cholesterol is an essential component of the human brain. In fact, the brain contains about 20% of the body’s entire supply of cholesterol. This fat is essential for the development and protection of nerve cells, which enable the brain to communicate with the rest of the body.

• #2 Patient education: High cholesterol and lipid treatment options (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/high-cholesterol-and-lipid-treatment-options-beyond-the-basics

  Some patients have extremely high levels of LDL cholesterol, eg, >190 mg/dL and a family history of others with such high levels. […] These patients often have a genetic factor that leads to a change in how cholesterol is processed in the body, and they have high levels of cholesterol from birth. […] Statins are one of the best-studied classes of medications and the most commonly used drugs for lowering LDL cholesterol. […] Statins decrease the body’s production of cholesterol and increase removal of cholesterol by the liver, so they reduce LDL cholesterol levels by as much as 25 to 55 percent. […] Statins may also reduce inflammation and may prevent heart attacks and strokes through this mechanism. […] Ezetimibe (brand name: Zetia) blocks the body’s ability to actively transport cholesterol from food as well as cholesterol that the body produces internally.

• #2 Patient education: High cholesterol and lipid treatment options (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/high-cholesterol-and-lipid-treatment-options-beyond-the-basics/print

  Bempedoic acid (brand name: Nexletol) is the newest lipid-lowering agent, and it is approved for lowering LDL cholesterol. […] Bempedoic acid alone or in combination with a statin or ezetimibe (brand name: Nexlizet) lowers LDL cholesterol as well as other atherogenic proteins. […] Statins are one of the best-studied classes of medications and the most commonly used drugs for lowering LDL cholesterol. […] Statins decrease the body’s production of cholesterol and increase removal of cholesterol by the liver, so they reduce LDL cholesterol levels by as much as 25 to 55 percent. […] Statins may also reduce inflammation and may prevent heart attacks and strokes through this mechanism.

• #2 Ezetimibe (Zetia): Uses, Side Effects, Interactions, Pictures, Warnings & Dosing – WebMD

  https://www.webmd.com/drugs/2/drug-64335/ezetimibe-oral/details

  Ezetimibe works by inhibiting the absorption of cholesterol in the intestines. Reduction of cholesterol absorption leads to lower cholesterol stores in the liver, which increases the removal of cholesterol from the bloodstream. […] To lower bad cholesterol levels (LDL-C) in people with high cholesterol levels. […] To lower bad cholesterol levels (LDL-C) in people that are born with a genetic condition affecting how the body removes cholesterol from the blood (heterozygous familial hypercholesterolemia or homozygous familial hypercholesterolemia) and in people with mixed hyperlipidemia (elevated cholesterol and triglycerides).

• #2 Patient education: High cholesterol and lipid treatment options (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/high-cholesterol-and-lipid-treatment-options-beyond-the-basics

  PCSK9 monoclonal antibody inhibitors are another class of drugs that lower LDL cholesterol levels. […] Bempedoic acid (brand name: Nexletol) is the newest lipid-lowering agent, and it is approved for lowering LDL cholesterol. […] Red yeast rice contains naturally occurring substances called monacolins that act to reduce cholesterol by a mechanism similar to that of statins. […] Plant stanols and sterols may act by blocking the absorption of cholesterol in the intestine.

• #2 Molecular mechanism of LDL cholesterol regulation | French national synchrotron facility

  https://www.synchrotron-soleil.fr/en/news/molecular-mechanism-ldl-cholesterol-regulation

  Inhibiting PCSK9 would then prevent the degradation of the various related proteins (see above), which would then increase the amount of HLA-C on the surface of the cells. HLA-C allows the recognition of „self” and stimulates the antitumor activity of T cells, hence the protective effect of PCSK9 inhibition against tumor growth and associated metastasis. […] Ultimately, the hope is to develop inhibitors that would prevent the interaction of PCSK9 and HLA-C and block the function of PCSK9 on LDLR and HLA-C.

• #2 Patient education: High cholesterol and lipid treatment options (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/high-cholesterol-and-lipid-treatment-options-beyond-the-basics

  A high cholesterol level (also called „hypercholesterolemia”) can significantly increase your risk of developing chest pain, heart attack, and stroke. […] Higher levels of LDL cholesterol are associated with greater risk of heart attack, stroke, need for stenting or coronary bypass surgery, and death. […] Studies over the past 50 years have shown that lowering LDL cholesterol leads to lower rates of these cardiac events. […] Cholesterol levels (notably LDL cholesterol and triglycerides) can almost always be lowered with a combination of weight loss (achieved with diet and exercise), and medications. […] As your level decreases, so does your risk of developing cardiovascular disease (CVD), including disease of the blood vessels supplying the heart (coronary artery disease), brain (cerebrovascular disease), and limbs (peripheral vascular disease).

• #2 Patient education: High cholesterol and lipid treatment options (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/high-cholesterol-and-lipid-treatment-options-beyond-the-basics

  The decision to start cholesterol-lowering treatment is made on a case-by-case basis. […] Studies have shown that in people with coronary heart disease, taking medication to significantly lower the level of „bad” cholesterol, called low-density lipoprotein (LDL) cholesterol, is beneficial. […] Many health care providers recommend treating anyone with CVD (including people who have coronary heart disease or have had a stroke) with high-dose statin therapy. […] If the LDL cholesterol is reduced to less than 70 mg/dL and preferably less than 55 mg/dL, the size of the plaques can get smaller. […] People with diabetes (type 1 or 2) are at high risk of heart disease. […] A moderate- or high-intensity statin is recommended in most adults with diabetes, regardless of their baseline LDL cholesterol level.

• #2 Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01125-5

  Disturbed cholesterol homeostasis plays critical roles in the development of multiple diseases, such as cardiovascular diseases (CVD), neurodegenerative diseases and cancers, particularly the CVD in which the accumulation of lipids (mainly the cholesteryl esters) within macrophage/foam cells underneath the endothelial layer drives the formation of atherosclerotic lesions eventually. […] Maintaining cholesterol homeostasis is determined by cholesterol biosynthesis, uptake, efflux, transport, storage, utilization, and/or excretion. All the processes should be precisely controlled by the multiple regulatory pathways. […] Mounting evidence has established the intricate link between cholesterol levels and atherosclerotic cardiovascular disease (ASCVD). […] Accumulation of cholesterol in atherosclerotic plaques may lead to formation of cholesterol crystals, a hallmark of advanced atherosclerotic plaques.

• #2 Cholesterol | MedlinePlus

  https://medlineplus.gov/cholesterol.html

  Cholesterol is a waxy, fat-like substance that’s found in all the cells in your body. Your body needs some cholesterol to make hormones, vitamin D, and substances that help you digest foods. Your body makes all the cholesterol it needs. Cholesterol is also found in foods from animal sources, such as egg yolks, meat, and cheese. […] If you have too much cholesterol in your blood, it can combine with other substances in the blood to form plaque. Plaque sticks to the walls of your arteries. This buildup of plaque is known as atherosclerosis. It can lead to coronary artery disease, a condition in which your coronary arteries become narrow or even blocked. […] The most common cause of high cholesterol is an unhealthy lifestyle. This can include: Unhealthy eating habits, such as eating lots of saturated fats. These fats are found in red meats, full-fat dairy products, chocolate, some baked goods, and many deep-fried and processed foods. Eating too much saturated fat can raise your LDL (bad) cholesterol.

• #2 What is the role of lipids in atherosclerosis and how low should we decrease lipid levels?

  https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-18/what-is-the-role-of-lipids-in-atherosclerosis-and-how-low-should-we-decrease-lip

  According to the response-to-retention concept, the key initiating event in atherogenesis is the retention of these cholesterol-rich apoB-containing lipoproteins within the arterial wall, particularly in the presence of endothelial dysfunction. […] Following their retention in the arterial wall, lipoproteins undergo modifications and ultimately trigger a series of maladaptive responses that accelerate further lipoprotein retention and cause further plaque progression. […] This process is facilitated by modification of the LDL particle by non-oxidative alteration, oxidation, glycosylation, or glycooxidation. […] In addition to facilitating uptake by macrophages and ultimately foam cell formation, oxidised LDL particles promote atherosclerosis via endothelial dysfunction. […] Retained LDL particles promote inflammatory and immune changes via cytokine release from macrophages, promoting further recruitment of immuno-inflammatory cells.

• #2 The Nobel Prize in Physiology or Medicine 1985 – Press release – NobelPrize.org

  https://www.nobelprize.org/prizes/medicine/1985/press-release/

  Brown and Goldstein have introduced entirely new principles for treatment of FH based on their discovery of the LDL-receptor. […] The discoveries made by Brown and Goldstein have drastically widened our understanding of the cholesterol metabolism and increased our possibilities to prevent and treat atherosclerosis and heart attacks.

• #3 What Is the Mechanism of Cholesterol Synthesis in the Liver?

  https://www.healthyjeenasikho.com/post/mechanism-of-cholesterol-synthesis?srsltid=AfmBOooUWB7PDEDbOD3zb6C6-uBcYsCv4KKlO2ABoly99gNyHTu5MLGC

  Sterol regulatory element-binding proteins (SREBPs) are important in cholesterol synthesis. These transcription factors manipulate cellular cholesterol levels, modulating the expression of genes involved in the process. Elevated cholesterol levels inhibit SREBP activity, reducing cholesterol synthesis to prevent excessive accumulation. […] Synthesized cholesterol is bound to lipoproteins in the liver for transport to other tissues. These lipoproteins, such as low-density lipoprotein (LDL), distribute cholesterol to cells throughout the body. […] Hepatic synthesis of cholesterol is intricately balanced with uptake and excretion. Legal controls ensure that cholesterol levels remain in the right range to support cellular function without harm. […] The liver is an important organ in cholesterol production. It controls a wide range of chemical reactions and the mechanisms by which this is done. Various mechanisms tightly regulate the pathway from acetyl-CoA to fatty acid synthesis. Keeping cholesterol in balance is important for our overall well-being.

• #3 High-density lipoprotein – Wikipedia

  https://en.wikipedia.org/wiki/High-density_lipoprotein

  High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are typically composed of 80-100 proteins per particle (organized by one, two or three ApoA). HDL particles enlarge while circulating in the blood, aggregating more fat molecules and transporting up to hundreds of fat molecules per particle. […] HDL particles are commonly referred to as „good cholesterol”, because they transport fat molecules out of artery walls, reduce macrophage accumulation, and thus help prevent or even regress atherosclerosis. […] HDL particles remove fats and cholesterol from cells, including within artery wall atheroma, and transport it back to the liver for excretion or re-use. Increasing concentrations of HDL particles in the blood are associated with decreasing accumulation of atherosclerosis within the walls of arteries, reducing the risk of sudden plaque ruptures, cardiovascular disease, stroke and other vascular diseases.

• #3 What is Familial Hypercholesterolemia? | American Heart Association

  https://www.heart.org/en/health-topics/cholesterol/genetic-conditions/familial-hypercholesterolemia-fh

  Familial hypercholesterolemia (FH) is an inherited defect in how the body recycles LDL, or “bad” cholesterol. […] High LDL contributes to plaque buildup, leading to a much higher-than-normal risk of coronary heart disease. If left untreated, people with FH have 20 times the risk of developing heart disease. […] Familial hypercholesterolemia is commonly caused by a mutation in the gene for the LDL cholesterol receptor, which is involved in passing LDL from the blood into cells for use by, or removal from, the body. […] FH remains underdiagnosed and undertreated. But people with FH have an excellent prognosis if the condition is identified early and treated. […] Familial hypercholesterolemia cannot be treated by diet and exercise alone. These lifestyle changes can help, but medications are recommended to reduce LDL cholesterol levels by at least 50%. […] Injectable medications, known as PCSK9 inhibitors, also can lower cholesterol levels. These medications target and block the PCSK9 protein, which frees up more receptors on liver cells to remove LDL cholesterol from the blood.

• #3 Polygenic Hypercholesterolemia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/121424-overview

  Familial hypercholesterolemia (FH) is sometimes clinically difficult to distinguish from polygenic hypercholesterolemia unless genetic testing is performed. […] Several drugs and disease states are associated with hypercholesterolemia; however, for the overwhelming majority of patients, the Western lifestyle of a high-fat diet superimposed on a susceptible genotype appears to cause hypercholesterolemia. […] The primary consequence of hypercholesterolemia is increased CHD risk. Data from epidemiological studies (eg, the Multiple Risk Factor Intervention Trial and the Framingham Heart Study) show a relationship between elevated LDL-C concentrations and CHD events and CHD mortality rates. […] The causative relationship between LDL-C levels and ischemic stroke and transient ischemic attack (TIA) was suggested by decreased cerebrovascular events in several major statin trials in which stroke was a secondary endpoint.

• #3 Cholesterol | MedlinePlus

  https://medlineplus.gov/cholesterol.html

  Cholesterol is a waxy, fat-like substance that’s found in all the cells in your body. Your body needs some cholesterol to make hormones, vitamin D, and substances that help you digest foods. Your body makes all the cholesterol it needs. Cholesterol is also found in foods from animal sources, such as egg yolks, meat, and cheese. […] If you have too much cholesterol in your blood, it can combine with other substances in the blood to form plaque. Plaque sticks to the walls of your arteries. This buildup of plaque is known as atherosclerosis. It can lead to coronary artery disease, a condition in which your coronary arteries become narrow or even blocked. […] The most common cause of high cholesterol is an unhealthy lifestyle. This can include: Unhealthy eating habits, such as eating lots of saturated fats. These fats are found in red meats, full-fat dairy products, chocolate, some baked goods, and many deep-fried and processed foods. Eating too much saturated fat can raise your LDL (bad) cholesterol.

• #3 Study Highlights Mechanism Connecting Diabetes, Elevated Cholesterol

  https://www.ajmc.com/view/study-highlights-mechanism-connecting-diabetes-elevated-cholesterol

  The connection between diabetes and cardiovascular disease is well-established. According to the American Heart Association, diabetes tends to lower high-density lipoprotein or good cholesterol, while increasing low-density lipoprotein (LDL) or bad cholesterol, thus increasing the likelihood of heart disease or stroke. […] Researchers from Helmholtz Zentrum Munchen, Technisch Universitat Munchen, known as TUM, conducted a series of experiments to uncover the mechanism that can cause hypercholesterolemia and increased lipid deposits in the arteries. […] The scientists demonstrated how TNF- signaling, via ROS, blocked GAbp. It turns out the liver protein is a regulator of another protein, AMPK, which controls levels of cholesterol. […] The work in this study shows the key role of GAbp as a regulator between inflammation, cholesterol homeostasis, and atherosclerosis, she said. Without the protective effect of GAbp, Niopek said, this leads to hypercholesterolemia, and increased lipid deposition in the arteries. […] Thus, inflammation in diabetes sets off a chain of events that elevates cholesterol causes atherosclerosis to develop over time, the researchers found.

• #3 What is the role of lipids in atherosclerosis and how low should we decrease lipid levels?

  https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-18/what-is-the-role-of-lipids-in-atherosclerosis-and-how-low-should-we-decrease-lip

  According to the response-to-retention concept, the key initiating event in atherogenesis is the retention of these cholesterol-rich apoB-containing lipoproteins within the arterial wall, particularly in the presence of endothelial dysfunction. […] Following their retention in the arterial wall, lipoproteins undergo modifications and ultimately trigger a series of maladaptive responses that accelerate further lipoprotein retention and cause further plaque progression. […] This process is facilitated by modification of the LDL particle by non-oxidative alteration, oxidation, glycosylation, or glycooxidation. […] In addition to facilitating uptake by macrophages and ultimately foam cell formation, oxidised LDL particles promote atherosclerosis via endothelial dysfunction. […] Retained LDL particles promote inflammatory and immune changes via cytokine release from macrophages, promoting further recruitment of immuno-inflammatory cells.

• #3 The Effects of Cholesterol on the Body

  https://www.healthline.com/health/cholesterol/effects-on-body

  Your body needs cholesterol to make hormones, vitamin D, and digestive fluids. However, too much of one type of cholesterol can contribute to cardiovascular disease and your risk of stroke. […] Cholesterol is a waxy substance found in your blood and in your cells. Your liver makes most of the cholesterol in your body. The rest comes from foods you eat. Cholesterol travels in your blood bundled up in packets called lipoproteins. […] When you have too much LDL cholesterol in your body, it can build up in your arteries, making them less flexible and potentially clogging them. Hardening of the arteries is called atherosclerosis. Blood doesn’t flow as well through stiff arteries, so your heart has to work harder to push blood through them. […] The buildup of plaque in the arteries can affect all organs, but more specifically, it can affect the heart, brain, and blood supply to the stomach, legs, or feet.

• #3 About Cholesterol | Cholesterol | CDC

  https://www.cdc.gov/cholesterol/about/index.html

  High cholesterol is having a total cholesterol above 200 mg/dL. […] Having high levels of LDL cholesterol can lead to plaque buildup in your arteries and result in heart disease or stroke. […] Having high blood cholesterol can lead to a buildup called „plaque” on the walls of your arteries (a type of blood vessel). […] High cholesterol also increases your risk for heart disease and stroke, two leading causes of death in the United States. […] Strong evidence shows that eating patterns that include less dietary cholesterol are associated with reduced risk of cardiovascular disease. […] Too much cholesterol puts you at risk for heart disease and stroke, two leading causes of death in the United States.

• #3 5 Diseases Linked to High Cholesterol

  https://www.webmd.com/cholesterol-management/diseases-linked-high-cholesterol

  If you have high cholesterol, you have a higher risk of cardiovascular disease. That can include coronary heart disease, stroke, and peripheral vascular disease. High cholesterol has also been tied to diabetes and high blood pressure. In all cases, the underlying cause is that high cholesterol leads to fatty plaques that build up in arteries all over your body. […] The main risk from high cholesterol is coronary heart disease, which can lead to death from a heart attack. If your cholesterol level is too high, cholesterol can build up in the walls of your arteries. Over time, this buildup — called plaque — causes arteries to harden and can restrict blood flow (atherosclerosis). […] Cholesterol plaques dont just line your blood vessels in and around your heart. They also narrow certain arteries that lead to your brain. If a vessel carrying blood to the brain is blocked completely, you could have a stroke.

• #3 Impact of Dietary Cholesterol on the Pathophysiology of Infectious and Autoimmune Disease

  https://www.mdpi.com/2072-6643/10/6/764

  In addition to regulating cellular signaling and inflammatory potential, lipid rafts serve as a point of pathogen association and colonization. […] Cholesterol is thought to mediate host cell infection by these Gram-negative bacterial strains through recognition and binding of the virulence factor cytolethal distending toxin (CDT), and mediating subsequent translocation of active toxin subunits. […] In addition to infectious disease pathways, cholesterol metabolism appears to play an important role in autoimmune disease. […] In patients with systemic lupus erythematous (SLE), T lymphocytes exhibit greater degrees of lipid raft formation and altered raft composition, leading to increased TCR-mediated signaling and inflammation. […] Dysregulation of lipid pathways may additionally contribute to inappropriate leukocyte activation and inflammation in autoimmune disorders. […] Taken together, research shows that lipid rafts and lipoprotein interactions are not only essential in the pathogenesis of infectious disease, but also in the compensatory immune response to ameliorate infection.

• #3 Cholesterol Efflux and Reverse Cholesterol Transport | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-319-09665-0_4

  Therefore, assessment of HDL function, evaluated as the capacity to promote cell cholesterol efflux may offer a better prediction of CVD than HDL levels alone. […] Consistent with this idea, it has been recently demonstrated that the evaluation of serum cholesterol efflux capacity (CEC) is a predictor of atherosclerosis extent in humans. […] The efflux process involves cholesterol localized on the plasma membrane that in turn may derive from intracellular sites, such as the late endosomal/lysosomal compartment and from the Golgi apparatus. […] Mechanisms accounting for cholesterol efflux include passive diffusion processes as well as active pathways mediated by ABCA1, ABCG1, and scavenger receptor class B type I (SR-BI). […] The nature of this process is a matter of debate: whereas this mechanism appears to be a relevant contributor of lipid removal in foam cell macrophages, the involvement of a still unknown transporter is not completely ruled out.

• #3 The mechanism of cholesterol action in the pathogenesis of Alzheimer’s disease – Ruđer BoÅ¡ković Institute

  https://www.irb.hr/eng/Divisions/Division-of-Molecular-Medicine/Laboratory-for-Neurodegenerative-Disease-Research/Projects/The-mechanism-of-cholesterol-action-in-the-pathogenesis-of-Alzheimer-s-disease

  Recent studies reveal that cholesterol may play a role in the pathogenesis of Alzheimers disease (AD). […] Treatment with cholesterol-lowering drugs (statins) appears to lower the risk of developing AD. […] Amyloid- (A) production is associated with cholesterol-rich domains (lipid rafts) and cholesterol levels modulate processing of -amyloid precursor protein (APP) and A generation. […] The goal of this project is to elucidate the mechanism(s) of cholesterol-effect on APP metabolism and the genesis of Alzheimers disease. […] We hypothesize that cholesterol modulates APP processing both directly and indirectly. […] We speculate that cholesterol regulation of membrane and protein trafficking along the endocytic pathway leads to amyloidogenic processing of APP. […] Lastly, we hypothesize that cholesterol metabolism is altered in patients with Alzheimers disease and that this effect is related to apoE genotype. […] Our findings may suggest that maintaining normal cholesterol homeostasis could protect and/or delay progression of Alzheimers disease.

• #3 The Role of Cholesterol in Chronic Lymphocytic Leukemia Development and Pathogenesis

  https://www.mdpi.com/2218-1989/13/7/799

  While there are conflicting reports concerning the role of cholesterol in CLL, there is clear evidence that cholesterol uptake and metabolism is disordered in CLL cells compared to healthy B-cells and other blood cancers, including acute lymphoblastic (ALL), acute myeloid (AML), and chronic myeloid leukemia (CML). […] Under normal physiological conditions, free cholesterol in the plasma membrane is not static and continuously shuttled between the cell interior and surface. […] CLL cells appear capable of overriding normal feedback mechanisms that regulate cholesterol levels, resulting in elevated intracellular levels of the lipid, a greater intracellular mass, modified membrane composition, and alterations in signaling pathways. […] Cholesterol is well recognized as an essential nutrient for cells throughout the body. It is an important precursor in the production of hormones, bile acids, and Vitamin D, and it is a critical structural component of cell membranes. […] Further studies concerning the potentially significant role of dietary cholesterol in CLL are also required, particularly as dietary intervention studies are relatively easy to conduct, with little risk to the patients.

• #3 High-density lipoprotein – Wikipedia

  https://en.wikipedia.org/wiki/High-density_lipoprotein

  People with higher levels of HDL-C tend to have fewer problems with cardiovascular diseases, while those with low HDL-C cholesterol levels (especially less than 40 mg/dL or about 1 mmol/L) have increased rates for heart disease. […] Higher native HDL levels are correlated with lowered risk of cardiovascular disease in healthy people. […] However, a higher blood level of HDL is not necessarily protective against cardiovascular disease and may even be harmful in extremely high quantities, with an increased cardiovascular risk, especially in hypertensive patients. […] Several steps in the metabolism of HDL can participate in the transport of cholesterol from lipid-laden macrophages of atherosclerotic arteries, termed foam cells, to the liver for secretion into the bile. This pathway has been termed reverse cholesterol transport and is considered as the classical protective function of HDL toward atherosclerosis.

• #3 Patient education: High cholesterol and lipid treatment options (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/high-cholesterol-and-lipid-treatment-options-beyond-the-basics

  Some patients have extremely high levels of LDL cholesterol, eg, >190 mg/dL and a family history of others with such high levels. […] These patients often have a genetic factor that leads to a change in how cholesterol is processed in the body, and they have high levels of cholesterol from birth. […] Statins are one of the best-studied classes of medications and the most commonly used drugs for lowering LDL cholesterol. […] Statins decrease the body’s production of cholesterol and increase removal of cholesterol by the liver, so they reduce LDL cholesterol levels by as much as 25 to 55 percent. […] Statins may also reduce inflammation and may prevent heart attacks and strokes through this mechanism. […] Ezetimibe (brand name: Zetia) blocks the body’s ability to actively transport cholesterol from food as well as cholesterol that the body produces internally.

• #3 Physiology, Cholesterol – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470561/

  As more lipid accumulates within the vessel wall, smooth muscle cells begin to migrate into the lesion. Ultimately, these smooth muscle cells encapsulate the newly formed plaque forming the fibrous plaque, the protector of the lesion, preventing the lipid core from being exposed to the lumen of the vessel. […] Hypercholesterolemia refers to the condition in which a patient has elevated blood concentrations of LDL-cholesterol. High LDL is of particular clinical importance, but it should be noted that hypercholesterolemia can also include very-low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL), i.e., non-HDL-cholesterol. […] Several factors can lead to increased LDL levels. Some of these factors include genetics, diet, stress, sedentary lifestyle, medications, and other disorders such as nephrotic syndrome and hypothyroidism.

• #3

  https://journals.lww.com/co-lipidology/fulltext/2016/10000/the_central_role_of_arterial_retention_of.6.aspx

  Today, it is no longer a hypothesis, but an established fact, that increased plasma concentrations of cholesterol-rich apolipoprotein-B (apoB)-containing lipoproteins are causatively linked to atherosclerotic cardiovascular disease (ASCVD) and that lowering plasma LDL concentrations reduces cardiovascular events in humans. […] Here, we review evidence behind this assertion, with an emphasis on recent studies supporting the response-to-retention model namely, that the key initiating event in atherogenesis is the retention, or trapping, of cholesterol-rich apoB-containing lipoproteins within the arterial wall. […] LDL and other cholesterol-rich, apoB-containing lipoproteins, once they become retained and modified within the arterial wall, cause atherosclerosis. This simple, robust pathophysiologic understanding may finally allow us to eradicate ASCVD, the leading killer in the world. […] After decades of research, however, there is now a large body of evidence to support the response-to-retention hypothesis namely, that the key initiating event in atherogenesis is the retention, or trapping, of cholesterol-rich apoB-containing lipoproteins within the arterial wall.

• #4 Cholesterol Efflux and Reverse Cholesterol Transport | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-319-09665-0_4

  The major mechanisms of cholesterol efflux are raft-independent. […] The non-raft membrane microdomains serve as the principal source of cholesterol available for interaction with extracellular acceptors and subsequent efflux via ATP-binding cassette transporter A1 (ABCA1) that is localized in these portions of the membrane. […] Interestingly, RCT can be triggered also from extracellular matrix-associated cholesterol microdomains, whose formation is mediated by ATP-binding cassette transporter G1 (ABCG1). […] Aqueous diffusion mainly involves free cholesterol in the plasma membrane and HDL as lipid acceptors. […] The expression of ABCA1 on the plasma membrane leads to the generation of non-raft microdomains and enlargement of cholesterol and phospholipid domains in the outer leaflet, thus facilitating the interaction with apoA-I and subsequent cholesterol efflux.

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