Materiały źródłowe

• #1 Cardiomyopathies 1: classification, pathophysiology and symptoms | Nursing Times

  https://www.nursingtimes.net/cardiovascular/cardiomyopathies-1-classification-pathophysiology-and-symptoms-17-06-2019/

  Cardiomyopathies are diseases characterised by structural and functional abnormalities of the myocardium. […] Advances in clinical and genomic medicine have led to better detection and understanding of cardiomyopathies (some of which have a strong genetic component), while high-profile cases of sudden cardiac death have increased awareness of the conditions. […] The American Heart Association describes cardiomyopathies as a heterogeneous group of diseases of the myocardium associated with mechanical and/or electric dysfunction that usually (but not invariably) exhibit inappropriate ventricular hypertrophy or dilatation due to a variety of etiologies that are frequently genetic. […] DCM can be caused by an inherent problem in the myocardium. Approximately 20-48% of cases are genetic […] Gene defects affecting structural elements in the cardiac muscle cells (cardiomyocytes), ion channels, cytoskeleton and mitochondria have been identified.

• #2 Understanding the Pathogenesis of Cardiomyopathy

  https://www.longdom.org/open-access/understanding-the-pathogenesis-of-cardiomyopathy-100174.html

  Understanding the Pathogenesis of Cardiomyopathy […] Cardiomyopathy is a condition characterized by damage or dysfunction of the heart muscle, which leads to impaired heart function and sometimes heart failure. The pathogenesis of cardiomyopathy is complex and multifactorial, involving genetic, environmental, and lifestyle factors that can interact and trigger a cascade of events leading to the development of the disease. […] Genetic mutations are known to play a significant role in the pathogenesis of cardiomyopathy. In many cases, cardiomyopathy can be inherited from one or both parents in an autosomal dominant pattern, meaning that only one copy of the mutated gene is required for the disease to manifest. […] Environmental factors, such as viral infections, toxins, and drugs, can also contribute to the pathogenesis of cardiomyopathy. […] Lifestyle factors, such as diet, exercise, and stress, can also impact the pathogenesis of cardiomyopathy. […] The pathophysiology of cardiomyopathy involves a complex interplay between genetic, environmental, and lifestyle factors that can trigger a cascade of events leading to the development of the disease. […] In conclusion, the pathogenesis of cardiomyopathy involves complex interactions between genetic, environmental and lifestyle factors, leading to structural changes in the heart muscle and impaired cardiac function.

• #3 Cardiomyopathies 1: classification, pathophysiology and symptoms | Nursing Times

  https://www.nursingtimes.net/cardiovascular/cardiomyopathies-1-classification-pathophysiology-and-symptoms-17-06-2019/

  Cardiomyopathies are diseases characterised by structural and functional abnormalities of the myocardium. […] Advances in clinical and genomic medicine have led to better detection and understanding of cardiomyopathies (some of which have a strong genetic component), while high-profile cases of sudden cardiac death have increased awareness of the conditions. […] The American Heart Association describes cardiomyopathies as a heterogeneous group of diseases of the myocardium associated with mechanical and/or electric dysfunction that usually (but not invariably) exhibit inappropriate ventricular hypertrophy or dilatation due to a variety of etiologies that are frequently genetic. […] DCM can be caused by an inherent problem in the myocardium. Approximately 20-48% of cases are genetic […] Gene defects affecting structural elements in the cardiac muscle cells (cardiomyocytes), ion channels, cytoskeleton and mitochondria have been identified.

• #4 Understanding the Pathogenesis of Cardiomyopathy

  https://www.longdom.org/open-access/understanding-the-pathogenesis-of-cardiomyopathy-100174.html

  Understanding the Pathogenesis of Cardiomyopathy […] Cardiomyopathy is a condition characterized by damage or dysfunction of the heart muscle, which leads to impaired heart function and sometimes heart failure. The pathogenesis of cardiomyopathy is complex and multifactorial, involving genetic, environmental, and lifestyle factors that can interact and trigger a cascade of events leading to the development of the disease. […] Genetic mutations are known to play a significant role in the pathogenesis of cardiomyopathy. In many cases, cardiomyopathy can be inherited from one or both parents in an autosomal dominant pattern, meaning that only one copy of the mutated gene is required for the disease to manifest. […] Environmental factors, such as viral infections, toxins, and drugs, can also contribute to the pathogenesis of cardiomyopathy. […] Lifestyle factors, such as diet, exercise, and stress, can also impact the pathogenesis of cardiomyopathy. […] The pathophysiology of cardiomyopathy involves a complex interplay between genetic, environmental, and lifestyle factors that can trigger a cascade of events leading to the development of the disease. […] In conclusion, the pathogenesis of cardiomyopathy involves complex interactions between genetic, environmental and lifestyle factors, leading to structural changes in the heart muscle and impaired cardiac function.

• #5 Cardiomyopathies: Evolution of pathogenesis concepts and potential for new therapies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4072838/

  Cardiomyopathies are defined as diseases of the myocardium with associated structural and functional abnormalities. […] Knowledge of the genotype of cardiomyopathies has changed the pathophysiological understanding of their etiology and clinical course, and has become more important in clinical practice for diagnosis and prevention of cardiomyopathies. […] New approaches for clinical and prognostic assessment are provided based on contemporary molecular mechanisms of contribution in the pathogenesis of cardiomyopathies. […] The MOGE(S) classification has several advantages with regard to simultaneous maximal description of disease from clinical and genetic points. However, this classification does not fulfill the diagnostic criteria of cardiomyopathies in several clinical situations and may not be always applied in clinical practice, because of the lack of genetic testing in many clinical centers.

• #6 Understanding the Pathogenesis of Cardiomyopathy

  https://www.longdom.org/open-access/understanding-the-pathogenesis-of-cardiomyopathy-100174.html

  Understanding the Pathogenesis of Cardiomyopathy […] Cardiomyopathy is a condition characterized by damage or dysfunction of the heart muscle, which leads to impaired heart function and sometimes heart failure. The pathogenesis of cardiomyopathy is complex and multifactorial, involving genetic, environmental, and lifestyle factors that can interact and trigger a cascade of events leading to the development of the disease. […] Genetic mutations are known to play a significant role in the pathogenesis of cardiomyopathy. In many cases, cardiomyopathy can be inherited from one or both parents in an autosomal dominant pattern, meaning that only one copy of the mutated gene is required for the disease to manifest. […] Environmental factors, such as viral infections, toxins, and drugs, can also contribute to the pathogenesis of cardiomyopathy. […] Lifestyle factors, such as diet, exercise, and stress, can also impact the pathogenesis of cardiomyopathy. […] The pathophysiology of cardiomyopathy involves a complex interplay between genetic, environmental, and lifestyle factors that can trigger a cascade of events leading to the development of the disease. […] In conclusion, the pathogenesis of cardiomyopathy involves complex interactions between genetic, environmental and lifestyle factors, leading to structural changes in the heart muscle and impaired cardiac function.

• #7 Molecular genetics and pathogenesis of cardiomyopathy | Journal of Human Genetics

  https://www.nature.com/articles/jhg201583

  The etiology of primary cardiomyopathy had been unknown, but various genetic abnormalities associated with the cardiomyopathy have recently been unraveled. […] Identification of the disease loci has enabled to decipher the disease-linked mutations in the genes located within the loci. […] The most important issue is the overlapping of disease genes for different clinical types. […] Mutations in genes for contractile elements have also been found in DCM patients. […] Initial analysis of functional changes caused by the MYH7 mutations demonstrated that contractile power generation was decreased in the presence of mutant myosin heavy chains and HCM-related mutations were found in other contractile elements, troponin T and -tropomyosin. […] However, the discovery of HCM-associated TNNI3 mutations at the contraction inhibitory domain implied that the decreased power might not be a common functional change caused by the contractile element mutations.

• #8 Cardiomyopathies 1: classification, pathophysiology and symptoms | Nursing Times

  https://www.nursingtimes.net/cardiovascular/cardiomyopathies-1-classification-pathophysiology-and-symptoms-17-06-2019/

  Cardiomyopathies are diseases characterised by structural and functional abnormalities of the myocardium. […] Advances in clinical and genomic medicine have led to better detection and understanding of cardiomyopathies (some of which have a strong genetic component), while high-profile cases of sudden cardiac death have increased awareness of the conditions. […] The American Heart Association describes cardiomyopathies as a heterogeneous group of diseases of the myocardium associated with mechanical and/or electric dysfunction that usually (but not invariably) exhibit inappropriate ventricular hypertrophy or dilatation due to a variety of etiologies that are frequently genetic. […] DCM can be caused by an inherent problem in the myocardium. Approximately 20-48% of cases are genetic […] Gene defects affecting structural elements in the cardiac muscle cells (cardiomyocytes), ion channels, cytoskeleton and mitochondria have been identified.

• #9 Cardiomyopathies 1: classification, pathophysiology and symptoms | Nursing Times

  https://www.nursingtimes.net/cardiovascular/cardiomyopathies-1-classification-pathophysiology-and-symptoms-17-06-2019/

  HCM is a heterogeneous disorder characterised by left ventricular hypertrophy and, in some cases, left ventricular outflow tract obstruction. […] A large number of genetic mutations in HCM have been described including those affecting proteins important for sarcomere function. […] Other causes of HCM include metabolic or neuromuscular diseases caused by genetic problems (5-10% of cases). […] RCM is suspected when patients have near-normal systolic function but diastolic dysfunction on echocardiography. […] There are several causes of RCM but in 50% no cause is identified. […] This genetic cardiomyopathy was first identified in 1700 in a family that had a specific dilation of the right ventricle. […] The condition is a significant cause of sudden cardiac death due to electric instability and subsequent ventricular tachycardia or ventricular fibrillation. […] Histiocytoid cardiomyopathy is thought to be caused by a developmental defect of the Purkinje cells, but findings of excessive numbers of abnormally shaped mitochondria in cardiac tissue suggest that mitochondrial dysfunction may play a role.

• #10 Molecular genetics and pathogenesis of cardiomyopathy | Journal of Human Genetics

  https://www.nature.com/articles/jhg201583

  Cardiomyopathy is defined as a disease of functional impairment in the cardiac muscle and its etiology includes both extrinsic and intrinsic factors. […] Genetic approaches have revealed the disease genes for hereditary primary cardiomyopathy and functional studies have demonstrated that characteristic functional alterations induced by the disease-associated mutations are closely related to the clinical types, such that increased and decreased Ca2+ sensitivities of muscle contraction are associated with HCM and DCM, respectively. […] Moreover, functional analysis of mutations in the other components of cardiac muscle have suggested that the altered response to metabolic stresses is associated with cardiomyopathy, further indicating the heterogeneity in the etiology and pathogenesis of cardiomyopathy.

• #11 Molecular genetics and pathogenesis of cardiomyopathy | Journal of Human Genetics

  https://www.nature.com/articles/jhg201583

  It should be noted here that drugs or chemicals that increased Ca2+ sensitivity could be effective in preventing heart failure in the mouse models carrying the DCM-associated TNNT2 mutation. […] Because the increased passive tension was associated with an increased Ca2+ sensitivity, it was speculated that HCM-associated abnormality in both Z-disc components and contractile elements might commonly result in the increased Ca2+ sensitivity of cardiac muscle. […] The loose sarcomere is evident in an animal model of DCM, a CSRP3 (MLP) knock-out mouse, in which Z-disc was wide and stretch response was impaired. […] Because the stretch response is a hypertrophic response of cardiomyocytes against passive tension and Z-disc elements have a role of stretch sensor in cardiomyocytes, abnormality in the Z-disc elements may alter the regulation of stretch response.

• #12 Hypertrophic Cardiomyopathy: Genetics, Pathogenesis, Diagnosis, Clinical Course and Therapy | IntechOpen

  https://www.intechopen.com/chapters/75983

  Hypertrophic cardiomyopathy (HCM) is a genetic disorder of cardiac myocytes that is characterized by cardiac hypertrophy, unexplained by the loading conditions, a non-dilated left ventricle and a normal or increased left ventricular ejection fraction (LV-EF). […] The precise mechanisms by which sarcomere variants result in the clinical phenotype have not been fully understood. Mutant sarcomere genes trigger several myocardial changes, leading to hypertrophy and fibrosis, which ultimately result in a small, stiff ventricle with impaired systolic and diastolic performance despite a preserved LV-EF. […] From a metabolic viewpoint, mutations in sarcomeric proteins generally increase myofilament activation and result in myocyte hypercontractility and excessive energy use due to higher (disproportionate) mitochondrial activity. Mitochondrial impairments in the cardiac energy-sensing apparatus as well as alterations in calcium handling result in a stimulation of signaling pathways that contribute to myocyte relaxation abnormalities and growth, with aberrant tissue architecture abnormalities such as myofibrillar disarray and myocardial fibrosis.

• #13 Hypertrophic Cardiomyopathy: Genetics, Pathogenesis, Diagnosis, Clinical Course and Therapy | IntechOpen

  https://www.intechopen.com/chapters/75983

  Hypertrophic cardiomyopathy (HCM) is a genetic disorder of cardiac myocytes that is characterized by cardiac hypertrophy, unexplained by the loading conditions, a non-dilated left ventricle and a normal or increased left ventricular ejection fraction (LV-EF). […] The precise mechanisms by which sarcomere variants result in the clinical phenotype have not been fully understood. Mutant sarcomere genes trigger several myocardial changes, leading to hypertrophy and fibrosis, which ultimately result in a small, stiff ventricle with impaired systolic and diastolic performance despite a preserved LV-EF. […] From a metabolic viewpoint, mutations in sarcomeric proteins generally increase myofilament activation and result in myocyte hypercontractility and excessive energy use due to higher (disproportionate) mitochondrial activity. Mitochondrial impairments in the cardiac energy-sensing apparatus as well as alterations in calcium handling result in a stimulation of signaling pathways that contribute to myocyte relaxation abnormalities and growth, with aberrant tissue architecture abnormalities such as myofibrillar disarray and myocardial fibrosis.

• #14 CAMZYOS® (mavacamten) Mechanism of Action | Safety Profile

  https://www.camzyoshcp.com/mechanism-of-action

  An excess of myosin-actin cross-bridges leads to structural changes in the left ventricle. […] The contractility and energy consumption of the heart are increased. […] The hearts ability to relax is impaired. […] Ultimately, the left ventricular wall thickens, resulting in a blockage or reduced blood flow. […] CAMZYOS is an allosteric and reversible inhibitor selective for cardiac myosin that helps to modulate the number of myosin heads in the off state. This reduces the number of myosin-actin cross-bridges that form. […] Reduced cardiac contractility. […] Reduced dynamic LVOT obstruction. […] Improved cardiac filling pressures. […] Improved energy consumption.

• #15 Advanced Evolution of Pathogenesis Concepts in Cardiomyopathies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6518034/

  Although several basic and clinical studies have investigated the mechanism of cardiomyopathy, the detailed pathophysiology remains unclear. […] The mutations impair cellular structures and muscle contraction via various pathways. Mutations in sarcomere proteins are important in RCM, accounting for 30% of the total cases, and include TTN, MYH7, MYH6, TNNT2, tropomyosin 1 (TPM1), and troponin C1 (TNNC1). […] Mutations in sarcomeric protein disrupt the mechanical property and the ability of muscle to contract and relax via calcium signaling in mechanotransduction pathways. […] The detailed mechanism of TTN-directed mechanotransduction signaling was investigated in recent cardiomyopathy studies. […] The dysfunction of the titin protein also induces defective transmission of force and transduction.

• #16 Advanced Evolution of Pathogenesis Concepts in Cardiomyopathies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6518034/

  Although several basic and clinical studies have investigated the mechanism of cardiomyopathy, the detailed pathophysiology remains unclear. […] The mutations impair cellular structures and muscle contraction via various pathways. Mutations in sarcomere proteins are important in RCM, accounting for 30% of the total cases, and include TTN, MYH7, MYH6, TNNT2, tropomyosin 1 (TPM1), and troponin C1 (TNNC1). […] Mutations in sarcomeric protein disrupt the mechanical property and the ability of muscle to contract and relax via calcium signaling in mechanotransduction pathways. […] The detailed mechanism of TTN-directed mechanotransduction signaling was investigated in recent cardiomyopathy studies. […] The dysfunction of the titin protein also induces defective transmission of force and transduction.

• #17 Advanced Evolution of Pathogenesis Concepts in Cardiomyopathies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6518034/

  Cardiomyopathy is a group of heterogeneous cardiac diseases that impair systolic and diastolic function, and can induce chronic heart failure and sudden cardiac death. […] Genetic mutations associated with cardiomyopathy play a key role in disease formation, especially the mutation of sarcomere encoding genes and ATP kinase genes, such as titin, lamin A/C, myosin heavy chain 7, and troponin T1. Pathogenesis of cardiomyopathy occurs by multiple complex steps involving several pathways, including the Ras-Raf-mitogen-activated protein kinase-extracellular signal-activated kinase pathway, G-protein signaling, mechanotransduction pathway, and protein kinase B/phosphoinositide 3-kinase signaling. Excess biomechanical stress induces apoptosis signaling in cardiomyocytes, leading to cell loss, which can induce myocardial fibrosis and remodeling.

• #18 Advanced Evolution of Pathogenesis Concepts in Cardiomyopathies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6518034/

  The resulting severe fibrosis disrupts the relaxation and contraction events, promotes stiffening of the myocardium, and induces chronic heart failure in cardiomyopathy. […] Several pathways are activated by biomechanical stress. Other growth factors, such as the Ras/Raf/MEK/ERK signaling pathway, G-protein signaling, Wnt/-catenin signaling pathway, AKT/PI3K pathway, TGF- signaling, JNK/MAPK pathway, and the apoptosis pathway, have been implicated in cardiomyopathy.

• #19 Advanced Evolution of Pathogenesis Concepts in Cardiomyopathies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6518034/

  The resulting severe fibrosis disrupts the relaxation and contraction events, promotes stiffening of the myocardium, and induces chronic heart failure in cardiomyopathy. […] Several pathways are activated by biomechanical stress. Other growth factors, such as the Ras/Raf/MEK/ERK signaling pathway, G-protein signaling, Wnt/-catenin signaling pathway, AKT/PI3K pathway, TGF- signaling, JNK/MAPK pathway, and the apoptosis pathway, have been implicated in cardiomyopathy.

• #20 Advanced Evolution of Pathogenesis Concepts in Cardiomyopathies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6518034/

  Cardiomyopathy is a group of heterogeneous cardiac diseases that impair systolic and diastolic function, and can induce chronic heart failure and sudden cardiac death. […] Genetic mutations associated with cardiomyopathy play a key role in disease formation, especially the mutation of sarcomere encoding genes and ATP kinase genes, such as titin, lamin A/C, myosin heavy chain 7, and troponin T1. Pathogenesis of cardiomyopathy occurs by multiple complex steps involving several pathways, including the Ras-Raf-mitogen-activated protein kinase-extracellular signal-activated kinase pathway, G-protein signaling, mechanotransduction pathway, and protein kinase B/phosphoinositide 3-kinase signaling. Excess biomechanical stress induces apoptosis signaling in cardiomyocytes, leading to cell loss, which can induce myocardial fibrosis and remodeling.

• #21 Cardiomyopathy – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/cardiomyopathy/symptoms-causes/syc-20370709

  Dilated cardiomyopathy causes the chambers of the heart to grow larger. Untreated, dilated cardiomyopathy can lead to heart failure. […] Often, the cause of the cardiomyopathy isn’t known. But some people get it due to another condition. This is known as acquired cardiomyopathy. Other people are born with cardiomyopathy because of a gene passed on from a parent. This is called inherited cardiomyopathy. […] Certain health conditions or behaviors that can lead to acquired cardiomyopathy include: Long-term high blood pressure. Heart tissue damage from a heart attack. Long-term rapid heart rate. Heart valve problems. COVID-19 infection. Certain infections, especially those that cause inflammation of the heart. Metabolic disorders, such as obesity, thyroid disease or diabetes. Lack of essential vitamins or minerals in the diet, such as thiamin (vitamin B-1). Pregnancy complications. Iron buildup in the heart muscle, called hemochromatosis. The growth of tiny lumps of inflammatory cells called granulomas in any part of the body. When this happens in the heart or lungs, it’s called sarcoidosis. The buildup of irregular proteins in the organs, called amyloidosis. Connective tissue disorders. Drinking too much alcohol over many years. Use of cocaine, amphetamines or anabolic steroids. Use of some chemotherapy medicines and radiation to treat cancer.

• #22 Cardiomyopathies: Evolution of pathogenesis concepts and potential for new therapies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4072838/

  The most typical DCM pattern is the development of interstitial and perivascular fibrosis of varying degree. […] The presence of significant non-compaction is estimated at 1:2000 in the general population. […] The condition may present without any associated cardiac malformation and is then labeled isolated LVNC. […] The condition is listed as an unclassified cardiomyopathy in the WHO and ESC classification of cardiomyopathies and as a primary genetic cardiomyopathy in the AHA classification. […] The presence of near-normal LV dimensions combined with increased myocardial wall thickness, particularly biventricular thickening, should arouse suspicion of an infiltrative cardiomyopathy, especially if accompanied by low-voltage QRS complexes on ECG. […] Myocardial relaxation abnormality with interstitial fibrosis and calcifications compose the fundamental abnormalities of restrictive cardiomyopathies. […] The treatment of restrictive cardiomyopathy patients is mainly symptomatic with diuretics and aldosterone antagonists.

• #23 Cardiomyopathy – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/cardiomyopathy/symptoms-causes/syc-20370709

  Dilated cardiomyopathy causes the chambers of the heart to grow larger. Untreated, dilated cardiomyopathy can lead to heart failure. […] Often, the cause of the cardiomyopathy isn’t known. But some people get it due to another condition. This is known as acquired cardiomyopathy. Other people are born with cardiomyopathy because of a gene passed on from a parent. This is called inherited cardiomyopathy. […] Certain health conditions or behaviors that can lead to acquired cardiomyopathy include: Long-term high blood pressure. Heart tissue damage from a heart attack. Long-term rapid heart rate. Heart valve problems. COVID-19 infection. Certain infections, especially those that cause inflammation of the heart. Metabolic disorders, such as obesity, thyroid disease or diabetes. Lack of essential vitamins or minerals in the diet, such as thiamin (vitamin B-1). Pregnancy complications. Iron buildup in the heart muscle, called hemochromatosis. The growth of tiny lumps of inflammatory cells called granulomas in any part of the body. When this happens in the heart or lungs, it’s called sarcoidosis. The buildup of irregular proteins in the organs, called amyloidosis. Connective tissue disorders. Drinking too much alcohol over many years. Use of cocaine, amphetamines or anabolic steroids. Use of some chemotherapy medicines and radiation to treat cancer.

• #24 Structures of PKA–phospholamban complexes reveal a mechanism of familial dilated cardiomyopathy | eLife

  https://elifesciences.org/articles/75346

  Our work supports a model in which the mutations at positions 9, 14, and 18 of PLN share a common disease mechanism. […] Lower phosphorylation levels of PLN in cardiac cells would lead to greater inhibition of SERCA, decreasing heart muscle contractility and relaxation rate. […] While catalytic efficiency of PKAc with PLN R9C only decreases by ~twofold, a corresponding change in phosphorylation level of PLN could be consistent with the relatively mild symptoms of DCM. […] The previously published crystal structure partially misguided attempts to understand how PKA regulates PLN.

• #25 Insight into the underlying molecular mechanism of dilated cardiomyopathy through integrative analysis of data mining, iTRAQ-PRM proteomics and bioinformatics | Proteome Science | Full Text

  https://proteomesci.biomedcentral.com/articles/10.1186/s12953-023-00214-9

  DCM is a common cardiomyopathy worldwide, which is characterized by ventricular dilatation and systolic dysfunction. […] However, our understanding of its molecular mechanisms is limited because of its etiology and underlying mechanisms. […] Hence, this study explored the underlying molecular mechanism of dilated cardiomyopathy through integrative analysis of data mining, iTRAQ-PRM proteomics and bioinformatics. […] The functional annotation of these DEPs revealed complicated molecular mechanisms including TCA cycle, Oxidative phosphorylation, Cardiac muscle contraction. […] Our results demonstrate that TCA cycle, Oxidative phosphorylation, Cardiac muscle contraction played important roles in the detailed molecular mechanisms of DCM. […] To date, the pathogenesis of DCM has not been fully clarified, but it has something to do mainly with changes in force transmission and force generation, metabolite changes, and abnormal ion channels.

• #26 Pathogenic Mechanisms of Hypertrophic Cardiomyopathy beyond Sarcomere Dysfunction

  https://www.mdpi.com/1422-0067/22/16/8933

  Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, affecting 1 in 500 people in the general population. […] While HCM is generally accepted as a disease of the sarcomere, variable penetrance in families with identical genetic mutations challenges the monogenic origin of HCM and instead implies a multifactorial cause. […] The etiology of HCM is thus likely multifactorial rather than strictly genetic. […] Mechanistically, at the molecular level, comprehensive characterization of animal models carrying various sarcomere gene mutations demonstrated dysfunctional cardiomyocyte excitation-contraction coupling as a driver of cardiomyocyte hypertrophy. […] However, whether other HCM-associated non-sarcomere gene mutations also promote cardiomyocyte hypertrophy through alteration in excitation-contraction coupling is not fully understood.

• #27 Cardiomyopathy – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/cardiomyopathy/symptoms-causes/syc-20370709

  Hypertrophic cardiomyopathy can start at any age. But it tends to be worse if it happens during childhood. Most people with this type of cardiomyopathy have a family history of the disease. Some gene changes have been linked to hypertrophic cardiomyopathy. The condition doesn’t happen due to a heart problem. […] Restrictive cardiomyopathy can occur for no known reason, also called an idiopathic cause. Or it can by caused by a disease elsewhere in the body that affects the heart, such as amyloidosis. […] Cardiomyopathy can lead to serious medical conditions, including: Heart failure. The heart can’t pump enough blood to meet the body’s needs. Without treatment, heart failure can be life-threatening. Blood clots. Because the heart can’t pump well, blood clots might form in the heart. If clots enter the bloodstream, they can block the blood flow to other organs, including the heart and brain. Heart valve problems. Because cardiomyopathy can cause the heart to become larger, the heart valves might not close properly. This can cause blood to flow backward in the valve. Cardiac arrest and sudden death. Cardiomyopathy can trigger irregular heart rhythms that cause fainting. Sometimes, irregular heartbeats can cause sudden death if the heart stops beating effectively.

• #28 Revealed: The molecular mechanism underlying hypertrophic cardiomyopathy, or

  https://scopeblog.stanford.edu/2018/08/14/revealed-the-molecular-mechanism-underlying-hypertrophic-cardiomyopathy-or-workaholic-heart/

  About one in every 500 of us is born with hypertrophic cardiomyopathy, a genetic disease caused by one of numerous mutations that, mysteriously, cause heart muscle to contract with too much force. […] Of the many mutations known to be able to cause hypertrophic cardiomyopathy, a preponderance — about 40 percent of them — occur in the gene coding for the particular variety of myosin found in heart muscle, leading Spudich to wonder what those mutations have in common. […] In a years-long effort culminating recently in a paper in the Proceedings of the National Academy of Sciences, Spudich and his labmates showed that many hypertrophic cardiomyopathy-associated mutations, although they occur at different points along the myosin gene’s sequence, often wind up affecting amino acids on the same surface of the folded protein’s outer edge, altering the myosin molecule in ways that coax it out of its “sleeping flamingo” posture. The changed postural preference, in turn, keeps a myosin molecule from spending enough time snoozing on the job, collectively causing constant overdrive in heart muscle’s power output.

• #29 FDA Extends Review Period for Aficamten in Obstructive Hypertrophic Cardiomyopathy

  https://www.empr.com/news/fda-extends-review-period-for-aficamten-in-obstructive-hypertrophic-cardiomyopathy/

  Aficamten is an oral, small molecule cardiac myosin inhibitor designed to reduce the number of active actin-myosin cross bridges during each cardiac cycle, thereby suppressing the myocardial hypercontractility associated with hypertrophic cardiomyopathy. […] Improvements in cardiac structure, function, and biomarkers were also reported in patients treated with aficamten. […] The REMS for mavacamten was established because of the potential risk for heart failure due to systolic dysfunction. According to Cytokinetics, none of the patients treated with aficamten in the SEQUOIA-HCM trial experienced this issue.

• #30 33 Hypertrophic cardiomyopathy: pathogenesis, therapies and disease modulation | Heart Asia

  https://heartasia.bmj.com/content/11/Suppl_1/A14

  Hypertrophic cardiomyopathy (HCM) is a prevalent heritable cardiac disorder, characterised by unexplained left ventricular hypertrophy (LVH) with the triad of myocyte hypertrophy, disarray, and interstitial fibrosis. […] Such pathological hallmarks impact diastolic function and contribute to adverse clinical outcomes: arrhythmias, progressive heart failure and sudden cardiac death. […] Multiple genetic studies have identified considerable numbers of HCM-causing mutations in human sarcomere protein genes, and mice engineered to carry such human mutations recapitulated key phenotypes of HCM. […] Studies in HCM mouse models have illustrated the importance of activated transforming growth factor beta (TGF-) pathway in the early development of HCM. […] Treatment with either TGF- neutralising antibodies or with angiotensin II type 1 receptor antagonist, losartan, was shown to retard and prevent HCM development in mouse models. […] Lately, MYK-461, the first allosteric inhibitor of the cardiac myosin adenosine triphosphate (ATPase), has been shown to reduce left ventricular contractility and attenuate HCM development in mouse models of HCM.

• #31 Cardiomyopathies 1: classification, pathophysiology and symptoms | Nursing Times

  https://www.nursingtimes.net/cardiovascular/cardiomyopathies-1-classification-pathophysiology-and-symptoms-17-06-2019/

  HCM is a heterogeneous disorder characterised by left ventricular hypertrophy and, in some cases, left ventricular outflow tract obstruction. […] A large number of genetic mutations in HCM have been described including those affecting proteins important for sarcomere function. […] Other causes of HCM include metabolic or neuromuscular diseases caused by genetic problems (5-10% of cases). […] RCM is suspected when patients have near-normal systolic function but diastolic dysfunction on echocardiography. […] There are several causes of RCM but in 50% no cause is identified. […] This genetic cardiomyopathy was first identified in 1700 in a family that had a specific dilation of the right ventricle. […] The condition is a significant cause of sudden cardiac death due to electric instability and subsequent ventricular tachycardia or ventricular fibrillation. […] Histiocytoid cardiomyopathy is thought to be caused by a developmental defect of the Purkinje cells, but findings of excessive numbers of abnormally shaped mitochondria in cardiac tissue suggest that mitochondrial dysfunction may play a role.

• #32 Cardiomyopathies 1: classification, pathophysiology and symptoms | Nursing Times

  https://www.nursingtimes.net/cardiovascular/cardiomyopathies-1-classification-pathophysiology-and-symptoms-17-06-2019/

  HCM is a heterogeneous disorder characterised by left ventricular hypertrophy and, in some cases, left ventricular outflow tract obstruction. […] A large number of genetic mutations in HCM have been described including those affecting proteins important for sarcomere function. […] Other causes of HCM include metabolic or neuromuscular diseases caused by genetic problems (5-10% of cases). […] RCM is suspected when patients have near-normal systolic function but diastolic dysfunction on echocardiography. […] There are several causes of RCM but in 50% no cause is identified. […] This genetic cardiomyopathy was first identified in 1700 in a family that had a specific dilation of the right ventricle. […] The condition is a significant cause of sudden cardiac death due to electric instability and subsequent ventricular tachycardia or ventricular fibrillation. […] Histiocytoid cardiomyopathy is thought to be caused by a developmental defect of the Purkinje cells, but findings of excessive numbers of abnormally shaped mitochondria in cardiac tissue suggest that mitochondrial dysfunction may play a role.

• #33 Cardiomyopathies: Evolution of pathogenesis concepts and potential for new therapies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4072838/

  The most typical DCM pattern is the development of interstitial and perivascular fibrosis of varying degree. […] The presence of significant non-compaction is estimated at 1:2000 in the general population. […] The condition may present without any associated cardiac malformation and is then labeled isolated LVNC. […] The condition is listed as an unclassified cardiomyopathy in the WHO and ESC classification of cardiomyopathies and as a primary genetic cardiomyopathy in the AHA classification. […] The presence of near-normal LV dimensions combined with increased myocardial wall thickness, particularly biventricular thickening, should arouse suspicion of an infiltrative cardiomyopathy, especially if accompanied by low-voltage QRS complexes on ECG. […] Myocardial relaxation abnormality with interstitial fibrosis and calcifications compose the fundamental abnormalities of restrictive cardiomyopathies. […] The treatment of restrictive cardiomyopathy patients is mainly symptomatic with diuretics and aldosterone antagonists.

• #34 Cardiomyopathies: Evolution of pathogenesis concepts and potential for new therapies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4072838/

  The most typical DCM pattern is the development of interstitial and perivascular fibrosis of varying degree. […] The presence of significant non-compaction is estimated at 1:2000 in the general population. […] The condition may present without any associated cardiac malformation and is then labeled isolated LVNC. […] The condition is listed as an unclassified cardiomyopathy in the WHO and ESC classification of cardiomyopathies and as a primary genetic cardiomyopathy in the AHA classification. […] The presence of near-normal LV dimensions combined with increased myocardial wall thickness, particularly biventricular thickening, should arouse suspicion of an infiltrative cardiomyopathy, especially if accompanied by low-voltage QRS complexes on ECG. […] Myocardial relaxation abnormality with interstitial fibrosis and calcifications compose the fundamental abnormalities of restrictive cardiomyopathies. […] The treatment of restrictive cardiomyopathy patients is mainly symptomatic with diuretics and aldosterone antagonists.

• #35 Advanced Evolution of Pathogenesis Concepts in Cardiomyopathies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6518034/

  Although several basic and clinical studies have investigated the mechanism of cardiomyopathy, the detailed pathophysiology remains unclear. […] The mutations impair cellular structures and muscle contraction via various pathways. Mutations in sarcomere proteins are important in RCM, accounting for 30% of the total cases, and include TTN, MYH7, MYH6, TNNT2, tropomyosin 1 (TPM1), and troponin C1 (TNNC1). […] Mutations in sarcomeric protein disrupt the mechanical property and the ability of muscle to contract and relax via calcium signaling in mechanotransduction pathways. […] The detailed mechanism of TTN-directed mechanotransduction signaling was investigated in recent cardiomyopathy studies. […] The dysfunction of the titin protein also induces defective transmission of force and transduction.

• #36 Arrhythmogenic right ventricular cardiomyopathy: Pathogenesis and genetics – UpToDate

  https://www.uptodate.com/contents/arrhythmogenic-right-ventricular-cardiomyopathy-pathogenesis-and-genetics

  Arrhythmogenic cardiomyopathy (ACM) is defined by a clinical presentation with documented or symptomatic arrhythmia and myocardial structural and functional abnormalities. […] The genetics and pathogenesis of ARVC will be reviewed here. […] Five established disease-causing genes in ARVC encode desmosomal proteins (plakoglobin, desmoplakin, plakophilin-2, desmoglein, and desmocollin in autosomal dominant disease and plakoglobin and desmoplakin in autosomal recessive disease) and support a new model for the pathogenesis of ARVC. Impaired desmosome function when subjected to mechanical stress causes myocyte detachment and cell death. The myocardial injury may be accompanied by inflammation. The presence of autoantibodies directed against elements of the intercalated disk is consistent with immune/autoimmune involvement. This raises the question as to whether inflammation contributes to disease progression or represents the initial phase of the repair process, which ultimately results in fibrofatty replacement of damaged myocytes.

• #37 Cardiomyopathies 1: classification, pathophysiology and symptoms | Nursing Times

  https://www.nursingtimes.net/cardiovascular/cardiomyopathies-1-classification-pathophysiology-and-symptoms-17-06-2019/

  HCM is a heterogeneous disorder characterised by left ventricular hypertrophy and, in some cases, left ventricular outflow tract obstruction. […] A large number of genetic mutations in HCM have been described including those affecting proteins important for sarcomere function. […] Other causes of HCM include metabolic or neuromuscular diseases caused by genetic problems (5-10% of cases). […] RCM is suspected when patients have near-normal systolic function but diastolic dysfunction on echocardiography. […] There are several causes of RCM but in 50% no cause is identified. […] This genetic cardiomyopathy was first identified in 1700 in a family that had a specific dilation of the right ventricle. […] The condition is a significant cause of sudden cardiac death due to electric instability and subsequent ventricular tachycardia or ventricular fibrillation. […] Histiocytoid cardiomyopathy is thought to be caused by a developmental defect of the Purkinje cells, but findings of excessive numbers of abnormally shaped mitochondria in cardiac tissue suggest that mitochondrial dysfunction may play a role.

• #38 Arrhythmogenic right ventricular cardiomyopathy: Pathogenesis and genetics – UpToDate

  https://www.uptodate.com/contents/arrhythmogenic-right-ventricular-cardiomyopathy-pathogenesis-and-genetics

  Arrhythmogenic cardiomyopathy (ACM) is defined by a clinical presentation with documented or symptomatic arrhythmia and myocardial structural and functional abnormalities. […] The genetics and pathogenesis of ARVC will be reviewed here. […] Five established disease-causing genes in ARVC encode desmosomal proteins (plakoglobin, desmoplakin, plakophilin-2, desmoglein, and desmocollin in autosomal dominant disease and plakoglobin and desmoplakin in autosomal recessive disease) and support a new model for the pathogenesis of ARVC. Impaired desmosome function when subjected to mechanical stress causes myocyte detachment and cell death. The myocardial injury may be accompanied by inflammation. The presence of autoantibodies directed against elements of the intercalated disk is consistent with immune/autoimmune involvement. This raises the question as to whether inflammation contributes to disease progression or represents the initial phase of the repair process, which ultimately results in fibrofatty replacement of damaged myocytes.

• #39

  https://link.springer.com/article/10.1007/s00395-020-0803-5

  Arrhythmogenic cardiomyopathy (AC) is an incurable genetic disease, whose pathogenesis is poorly understood. […] To elucidate AC pathogenesis and to design possible treatment strategies of AC, multiple murine models have been established. […] Using two mouse strains producing either a mutant desmoglein 2 or lacking desmoglein 2 in cardiomyocytes, we test the hypothesis that inflammation is a major component of disease pathogenesis. […] Together, our observations provide strong evidence that specific immune cell populations and chemokine expression profiles modulate inflammatory and repair processes throughout AC progression. […] It is has been reported that inflammation is a component of AC disease initiation and progression with multiple reports on the detection of immune cells in various disease stages.

• #40

  https://link.springer.com/article/10.1007/s00395-020-0803-5

  The goal of the current study was therefore to determine whether and how inflammation contributes to the different disease stages of murine AC and to dissect the cellular responses involved. […] It has been suggested that cardiomyocyte necrosis is the key pathogenic event triggering an inflammatory response in murine Dsg2-related AC. […] To further characterize the early inflammatory response, we assessed the mRNA expression of the chemokines Ccl2, Ccl3, and their respective receptors Ccr2 and Ccr5 that are known to be involved in the recruitment of mononuclear cells in ischemic myocardium. […] The recruitment and activation of different immune cell types are reflected in the upregulation of Ccl2-Ccl7-Ccl12/Ccr2, Ccl3/Ccr5, and Cx3cl1/Cx3cr1 and Cxcl10/Cxcr3 expression. […] Our observations further show, that cardiomyocyte necrosis is triggered during the most intense postnatal maturation and growth phase of the murine heart, i.e. between 2 and 6 weeks, and consistently activates a stereotypical inflammatory repair program, which also includes adverse effects on myocardial structure and function.

• #41 Molecular Basis of Inflammation in the Pathogenesis of Cardiomyopathies

  https://www.mdpi.com/1422-0067/21/18/6462

  The development and progression of a cardiomyopathic phenotype depends on a complex interaction between several cellular signaling pathways, environmental stressors and individual genotypes. Our understanding regarding the development and the progression of each cardiomyopathy has improved over the last decades. Among the several mechanisms implicated, inflammation seems to have an important role in the pathogenesis of CMPs. […] Myocardial inflammation has recently emerged as a pathophysiologic process that contributes to cardiac hypertrophy, fibrosis and dysfunction in the context of heart disease. Elevated inflammatory biomarkers represent a hallmark feature of both heart failure with a preserved ejection fraction and heart failure with a reduced ejection fraction. The “cytokine hypothesis” has postulated that heart failure progresses, at least in part, as a result of the deleterious effects of the endogenous cytokine cascades on the myocardium and the peripheral circulation.

• #42 Molecular Basis of Inflammation in the Pathogenesis of Cardiomyopathies

  https://www.mdpi.com/1422-0067/21/18/6462

  The development and progression of a cardiomyopathic phenotype depends on a complex interaction between several cellular signaling pathways, environmental stressors and individual genotypes. Our understanding regarding the development and the progression of each cardiomyopathy has improved over the last decades. Among the several mechanisms implicated, inflammation seems to have an important role in the pathogenesis of CMPs. […] Myocardial inflammation has recently emerged as a pathophysiologic process that contributes to cardiac hypertrophy, fibrosis and dysfunction in the context of heart disease. Elevated inflammatory biomarkers represent a hallmark feature of both heart failure with a preserved ejection fraction and heart failure with a reduced ejection fraction. The “cytokine hypothesis” has postulated that heart failure progresses, at least in part, as a result of the deleterious effects of the endogenous cytokine cascades on the myocardium and the peripheral circulation.

• #43 Molecular Basis of Inflammation in the Pathogenesis of Cardiomyopathies

  https://www.mdpi.com/1422-0067/21/18/6462

  Moreover, the evidence that CMPs, such as heart failure, can be associated with elevated circulating levels of proinflammatory cytokines has provided a new research area that has revealed a potential role of inflammation and immune system activation in the pathogenesis of these disorders. […] The persistent activation of cardiac inflammatory pathways may lead to significant fibrotic changes, which represent a substrate for pathological myocardial remodeling. Myocardial fibrosis results in electromechanical disturbances and reduces the nutrient supply toward the myocardium, perpetuating a vicious cycle of fibrosis, myocyte death and inflammation. […] The aim of the present review is to summarize the current knowledge on the role of inflammation and immune system activation in the pathogenesis of CMPs and to identify potential molecular targets for a tailored anti-inflammatory treatment.

• #44 Molecular Basis of Inflammation in the Pathogenesis of Cardiomyopathies

  https://www.mdpi.com/1422-0067/21/18/6462

  Moreover, the evidence that CMPs, such as heart failure, can be associated with elevated circulating levels of proinflammatory cytokines has provided a new research area that has revealed a potential role of inflammation and immune system activation in the pathogenesis of these disorders. […] The persistent activation of cardiac inflammatory pathways may lead to significant fibrotic changes, which represent a substrate for pathological myocardial remodeling. Myocardial fibrosis results in electromechanical disturbances and reduces the nutrient supply toward the myocardium, perpetuating a vicious cycle of fibrosis, myocyte death and inflammation. […] The aim of the present review is to summarize the current knowledge on the role of inflammation and immune system activation in the pathogenesis of CMPs and to identify potential molecular targets for a tailored anti-inflammatory treatment.

• #45 Immune-inflammatory concept of the pathogenesis of chronic heart failure in dogs with dilated cardiomyopathy

  http://www.veterinaryworld.org/Vol.12/September-2019/21.html

  Dilated cardiomyopathy is common in dogs. This form of cardiomyopathy is the main cause of death due to heart disease in dogs. […] The pathogenesis of heart failure syndrome in dogs with dilated cardiomyopathy involves activation of the neurohumoral system and immune-mediated inflammation, which leads to further progression of the condition. […] Heart failure syndrome in dogs with dilated cardiomyopathy is caused by the progressive loss of cardiomyocytes, apoptosis, remodeling of the left ventricle, systolic and diastolic dysfunction, arrhythmias, reduced cerebral blood flow, the involvement of other key internal organs, and intestinal dysbiosis. […] The central component of heart failure syndrome in dogs with dilated cardiomyopathy is the activation of the neurohumoral system and immune-mediated inflammation. The development of CHF in dogs with dilated cardiomyopathy is caused by the progressive loss of cardiomyocytes, apoptosis, remodeling of the left ventricle, systolic and diastolic dysfunction, arrhythmias, reduced cerebral blood flow, involvement of other key internal organs, and intestinal dysbiosis.

• #46

  https://journals.lww.com/eccm/fulltext/2022/09000/septic_cardiomyopathy__characteristics,.7.aspx

  Septic cardiomyopathy is a complication of sepsis-related cardiovascular failure, characterized by reversible left ventricular dilatation and decreased ventricular systolic and/or diastolic function. […] The pathogenesis of several septic cardiomyopathy has been clarified, such as immune response caused by infection and mitochondrial dysfunction. […] The pathogenesis of septic cardiomyopathy is very complex and may involve abnormal inflammatory responses, such as activation of myocardial inhibitors such as tumor necrosis factor (TNF-), interleukin 1 (IL-1), and interleukin 6 (IL-6); activation of the complement system; and mitochondrial dysfunction, such as the production of nitric oxide (NO) reactive oxygen species (ROS), oxidative stress, calcium overload, and so on. […] The imbalance of inflammatory response induced by sepsis is considered to be directly related to the occurrence of myocardial dysfunction.

• #47

  https://journals.lww.com/eccm/fulltext/2022/09000/septic_cardiomyopathy__characteristics,.7.aspx

  Septic cardiomyopathy is a complication of sepsis-related cardiovascular failure, characterized by reversible left ventricular dilatation and decreased ventricular systolic and/or diastolic function. […] The pathogenesis of several septic cardiomyopathy has been clarified, such as immune response caused by infection and mitochondrial dysfunction. […] The pathogenesis of septic cardiomyopathy is very complex and may involve abnormal inflammatory responses, such as activation of myocardial inhibitors such as tumor necrosis factor (TNF-), interleukin 1 (IL-1), and interleukin 6 (IL-6); activation of the complement system; and mitochondrial dysfunction, such as the production of nitric oxide (NO) reactive oxygen species (ROS), oxidative stress, calcium overload, and so on. […] The imbalance of inflammatory response induced by sepsis is considered to be directly related to the occurrence of myocardial dysfunction.

• #48 Arrhythmogenic right ventricular cardiomyopathy: Pathogenesis and genetics – UpToDate

  https://www.uptodate.com/contents/arrhythmogenic-right-ventricular-cardiomyopathy-pathogenesis-and-genetics

  Arrhythmogenic cardiomyopathy (ACM) is defined by a clinical presentation with documented or symptomatic arrhythmia and myocardial structural and functional abnormalities. […] The genetics and pathogenesis of ARVC will be reviewed here. […] Five established disease-causing genes in ARVC encode desmosomal proteins (plakoglobin, desmoplakin, plakophilin-2, desmoglein, and desmocollin in autosomal dominant disease and plakoglobin and desmoplakin in autosomal recessive disease) and support a new model for the pathogenesis of ARVC. Impaired desmosome function when subjected to mechanical stress causes myocyte detachment and cell death. The myocardial injury may be accompanied by inflammation. The presence of autoantibodies directed against elements of the intercalated disk is consistent with immune/autoimmune involvement. This raises the question as to whether inflammation contributes to disease progression or represents the initial phase of the repair process, which ultimately results in fibrofatty replacement of damaged myocytes.

• #49 Pathogenesis and Pharmacology of Metabolic Cardiomyopathy | Frontiers Research Topic

  https://www.frontiersin.org/research-topics/44229/pathogenesis-and-pharmacology-of-metabolic-cardiomyopathyundefined

  Metabolic cardiomyopathy (MeC) is a special type of cardiovascular disease caused by systematic metabolic disorders inherited or acquired during adulthood. […] Understanding the molecular mechanism of MeC and developing therapeutic approaches that can improve the outcome of patients with MeC represent the forefront of cardiovascular research. […] The primary objective is to comprehensively summarize the current perspectives and propose future research directions regarding genetics, diagnosis, staging, classification, mechanisms, new models, new methodologies, etiology or risk factors, prevention, and treatment of MeCs including diabetic cardiomyopathy, myocardial ischemia reperfusion, and hypertension cardiomyopathy, etc. […] 1. Molecular Mechanism and/or Pharmacology of Diabetic cardiomyopathy. 2. Molecular Mechanism and/or Pharmacology of myocardial ischemia reperfusion. 3. Molecular Mechanism and/or Pharmacology of hypertension cardiomyopathy.

• #50 Pathogenesis and Pharmacology of Metabolic Cardiomyopathy | Frontiers Research Topic

  https://www.frontiersin.org/research-topics/44229/pathogenesis-and-pharmacology-of-metabolic-cardiomyopathyundefined

  Metabolic cardiomyopathy (MeC) is a special type of cardiovascular disease caused by systematic metabolic disorders inherited or acquired during adulthood. […] Understanding the molecular mechanism of MeC and developing therapeutic approaches that can improve the outcome of patients with MeC represent the forefront of cardiovascular research. […] The primary objective is to comprehensively summarize the current perspectives and propose future research directions regarding genetics, diagnosis, staging, classification, mechanisms, new models, new methodologies, etiology or risk factors, prevention, and treatment of MeCs including diabetic cardiomyopathy, myocardial ischemia reperfusion, and hypertension cardiomyopathy, etc. […] 1. Molecular Mechanism and/or Pharmacology of Diabetic cardiomyopathy. 2. Molecular Mechanism and/or Pharmacology of myocardial ischemia reperfusion. 3. Molecular Mechanism and/or Pharmacology of hypertension cardiomyopathy.

• #51 Ferroptosis: A New Mechanism in Diabetic Cardiomyopathy

  https://www.medsci.org/v21p0612.htm

  Diabetic cardiomyopathy (DC) is a pathophysiologic condition caused by diabetes mellitus (DM) in the absence of coronary artery disease, valvular heart disease, and hypertension that can lead to heart failure (HF), manifesting itself in the early stages with left ventricular hypertrophy and diastolic dysfunction, with marked HF and decreased systolic function in the later stages. […] Ferroptosis is a novel form of cell death characterized by reactive oxygen species (ROS) accumulation and lipid peroxidation. Several cell and animal studies have shown that ferroptosis is closely related to DC progression. This review systematically summarizes the related pathogenic mechanisms of ferroptosis in DC, including the reduction of cardiac RDH10 induced ferroptosis in DC cardiomyocytes which mediated by retinol metabolism disorders; CD36 overexpression caused lipid deposition and decreased GPX4 expression in DC cardiomyocytes, leading to the development of ferroptosis; Nrf2 mediated iron overload and lipid peroxidation in DC cardiomyocytes and promoted ferroptosis; lncRNA-ZFAS1 as a ceRNA, combined with miR-150-5p to inhibit CCND2 expression in DC cardiomyocytes, thereby triggering ferroptosis.

• #52 Ferroptosis: A New Mechanism in Diabetic Cardiomyopathy

  https://www.medsci.org/v21p0612.htm

  CD36 could up-regulate ACSL4 and P53, down-regulate the mRNA and protein expression of Gpx4, promote ROS production, enhance intracellular lipid deposition, and lead to ferroptosis in DC cardiomyocytes, resulting in myocardial injury and cardiac dysfunction in vivo and in vitro experiments. […] Nrf2 mediated iron overload and lipid peroxidation in DC cardiomyocytes and promoted ferroptosis. […] ZFAS1, as ceRNA bound to miR-150-5p, decreased CCND2 expression levels contributing to ferroptosis and DC development in cardiomyocytes.

• #53 MCT4-dependent lactate transport: a novel mechanism for cardiac energy metabolism injury and inflammation in type 2 diabetes mellitus | Cardiovascular Diabetology | Full Text

  https://cardiab.biomedcentral.com/articles/10.1186/s12933-024-02178-2

  Diabetic cardiomyopathy (DCM) is a major contributor to mortality in diabetic patients, characterized by a multifaceted pathogenesis and limited therapeutic options. […] The pathogenesis of DCM encompasses a multitude of intricate biological mechanisms, encompassing aberrant energy metabolism and subsequent oxidative stress, endoplasmic reticulum stress, inflammation, apoptosis, and fibrosis. […] Our findings highlight the pivotal involvement of MCT4 in the dysregulation of cardiac energy metabolism and macrophage-mediated inflammation in type 2 diabetes. […] These insights offer novel perspectives on the pathogenesis of DCM and pave the way for the development of targeted therapeutic strategies against this debilitating condition. […] Our findings uncovered an upregulation of key differential genes encoding MCT4, a crucial lactate transporter.

• #54 MCT4-dependent lactate transport: a novel mechanism for cardiac energy metabolism injury and inflammation in type 2 diabetes mellitus | Cardiovascular Diabetology | Full Text

  https://cardiab.biomedcentral.com/articles/10.1186/s12933-024-02178-2

  These discoveries strongly implicate the upregulated expression of MCT4 as a potential key factor in the development of DCM. […] These findings suggest that MCT4 upregulation may mediate the imbalance of the lactate-pyruvate axis induced by fatty acids, ultimately leading to mitochondrial oxidative stress damage in cardiomyocytes. […] Our research indicates that lactic acid can simultaneously induce H3K18La and H4K12La in macrophages. […] Our findings suggest that the inhibition of MCT4 plays a significant role in alleviating cardiac inflammation in type 2 diabetic mice. […] Our comprehensive investigation has unveiled the pivotal role of MCT4-dependent lactic acid transport in mediating energy metabolism impairments and inflammatory responses in the hearts of type 2 diabetes, thereby confirming the protective effects of MCT4 inhibition in DCM.

• #55 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20201119/Research-on-genetic-heart-disease-uncovers-new-mechanism-for-heart-failure.aspx

  Research on genetic heart disease has uncovered a new and unexpected mechanism for heart failure. […] However, the new discovery finds another way that mutant RBM20 damages heart muscle cells: through an accumulation of pathological ribonucleoprotein granules, affecting everything in the cells and leading to a new form of the disease. […] This supports a new concept that beyond splicing caused by the gene mutation, RBM20 is an RNA-binding protein granule disease similar to diseases like Lou Gehrig’s disease, or amyotrophic lateral sclerosis, and Alzheimer’s disease. […] Most importantly, we can study and develop therapies to prevent the buildup of these toxic granules at the beginning of life instead of waiting 50 years or more for a degenerative disease to appear clinically. This is a huge advantage that should accelerate drug discovery in ribonucleoprotein granule degenerative diseases of the heart and nervous system.

• #56 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20201119/Research-on-genetic-heart-disease-uncovers-new-mechanism-for-heart-failure.aspx

  Research on genetic heart disease has uncovered a new and unexpected mechanism for heart failure. […] However, the new discovery finds another way that mutant RBM20 damages heart muscle cells: through an accumulation of pathological ribonucleoprotein granules, affecting everything in the cells and leading to a new form of the disease. […] This supports a new concept that beyond splicing caused by the gene mutation, RBM20 is an RNA-binding protein granule disease similar to diseases like Lou Gehrig’s disease, or amyotrophic lateral sclerosis, and Alzheimer’s disease. […] Most importantly, we can study and develop therapies to prevent the buildup of these toxic granules at the beginning of life instead of waiting 50 years or more for a degenerative disease to appear clinically. This is a huge advantage that should accelerate drug discovery in ribonucleoprotein granule degenerative diseases of the heart and nervous system.

• #57 Inline perfusion mapping provides insights into the disease mechanism in hypertrophic cardiomyopathy | Heart

  https://heart.bmj.com/content/106/11/824

  In patients with hypertrophic cardiomyopathy (HCM), the role of small vessel disease and myocardial perfusion remains incompletely understood and data on absolute myocardial blood flow (MBF, mL/g/min) are scarce. […] Microvascular dysfunction is common in HCM and associated with hypertrophy and LGE. Perfusion can fall during vasodilator stress and is abnormal even in apparently normal myocardium suggesting it may be an early disease marker. […] The histological features are myocyte disarray, left (right) ventricular hypertrophy (LVH), small vessel disease and fibrosis, but how these features develop and relate to adverse outcomes is poorly understood. […] Ischaemia in HCM is likely a key disease pathway. […] Several mechanisms may contribute to ischaemia in HCM including small vessel abnormalities, demand-supply mismatch due to hypertrophy, reduced perfusion pressure related to shortened diastolic time, high diastolic pressure, left ventricular outflow tract (LVOT) obstruction and possibly myocardial bridging.

• #58 Inline perfusion mapping provides insights into the disease mechanism in hypertrophic cardiomyopathy | Heart

  https://heart.bmj.com/content/106/11/824

  In patients with hypertrophic cardiomyopathy (HCM), the role of small vessel disease and myocardial perfusion remains incompletely understood and data on absolute myocardial blood flow (MBF, mL/g/min) are scarce. […] Microvascular dysfunction is common in HCM and associated with hypertrophy and LGE. Perfusion can fall during vasodilator stress and is abnormal even in apparently normal myocardium suggesting it may be an early disease marker. […] The histological features are myocyte disarray, left (right) ventricular hypertrophy (LVH), small vessel disease and fibrosis, but how these features develop and relate to adverse outcomes is poorly understood. […] Ischaemia in HCM is likely a key disease pathway. […] Several mechanisms may contribute to ischaemia in HCM including small vessel abnormalities, demand-supply mismatch due to hypertrophy, reduced perfusion pressure related to shortened diastolic time, high diastolic pressure, left ventricular outflow tract (LVOT) obstruction and possibly myocardial bridging.

• #59 Inline perfusion mapping provides insights into the disease mechanism in hypertrophic cardiomyopathy | Heart

  https://heart.bmj.com/content/106/11/824

  In patients with hypertrophic cardiomyopathy (HCM), the role of small vessel disease and myocardial perfusion remains incompletely understood and data on absolute myocardial blood flow (MBF, mL/g/min) are scarce. […] Microvascular dysfunction is common in HCM and associated with hypertrophy and LGE. Perfusion can fall during vasodilator stress and is abnormal even in apparently normal myocardium suggesting it may be an early disease marker. […] The histological features are myocyte disarray, left (right) ventricular hypertrophy (LVH), small vessel disease and fibrosis, but how these features develop and relate to adverse outcomes is poorly understood. […] Ischaemia in HCM is likely a key disease pathway. […] Several mechanisms may contribute to ischaemia in HCM including small vessel abnormalities, demand-supply mismatch due to hypertrophy, reduced perfusion pressure related to shortened diastolic time, high diastolic pressure, left ventricular outflow tract (LVOT) obstruction and possibly myocardial bridging.

• #60 Inline perfusion mapping provides insights into the disease mechanism in hypertrophic cardiomyopathy | Heart

  https://heart.bmj.com/content/106/11/824

  The evidence base for quantitative perfusion CMR is more limited but increasing in recent years. […] However, these associations were relatively modest, and even myocardial segments without LVH or LGE had impaired perfusion, suggesting that microvascular dysfunction is substantially independent of macroscopic scar and hypertrophy, and may be an important marker in early HCM. […] A striking finding was that stress flow in HCM could be paradoxically lower than rest in HCM. […] In conclusion, using fully quantitative CMR perfusion mapping incorporated into a clinical workflow, we have demonstrated the role of microvascular dysfunction in HCM and that while this is statistically strongly associated with regional hypertrophy and fibrosis, these processes explain only a small amount of myocardial stress blood flow heterogeneity.

• #61 Inline perfusion mapping provides insights into the disease mechanism in hypertrophic cardiomyopathy | Heart

  https://heart.bmj.com/content/106/11/824

  The evidence base for quantitative perfusion CMR is more limited but increasing in recent years. […] However, these associations were relatively modest, and even myocardial segments without LVH or LGE had impaired perfusion, suggesting that microvascular dysfunction is substantially independent of macroscopic scar and hypertrophy, and may be an important marker in early HCM. […] A striking finding was that stress flow in HCM could be paradoxically lower than rest in HCM. […] In conclusion, using fully quantitative CMR perfusion mapping incorporated into a clinical workflow, we have demonstrated the role of microvascular dysfunction in HCM and that while this is statistically strongly associated with regional hypertrophy and fibrosis, these processes explain only a small amount of myocardial stress blood flow heterogeneity.

• #62 Cardiomyopathy – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/cardiomyopathy/symptoms-causes/syc-20370709

  Hypertrophic cardiomyopathy can start at any age. But it tends to be worse if it happens during childhood. Most people with this type of cardiomyopathy have a family history of the disease. Some gene changes have been linked to hypertrophic cardiomyopathy. The condition doesn’t happen due to a heart problem. […] Restrictive cardiomyopathy can occur for no known reason, also called an idiopathic cause. Or it can by caused by a disease elsewhere in the body that affects the heart, such as amyloidosis. […] Cardiomyopathy can lead to serious medical conditions, including: Heart failure. The heart can’t pump enough blood to meet the body’s needs. Without treatment, heart failure can be life-threatening. Blood clots. Because the heart can’t pump well, blood clots might form in the heart. If clots enter the bloodstream, they can block the blood flow to other organs, including the heart and brain. Heart valve problems. Because cardiomyopathy can cause the heart to become larger, the heart valves might not close properly. This can cause blood to flow backward in the valve. Cardiac arrest and sudden death. Cardiomyopathy can trigger irregular heart rhythms that cause fainting. Sometimes, irregular heartbeats can cause sudden death if the heart stops beating effectively.

• #63

  https://link.springer.com/article/10.1007/s11897-022-00568-9

  Chagas disease is a neglected anthropozoonosis of global importance with significant cardiovascular-associated mortality. This review focuses on the Trypanosoma cruzi reinfections role in chronic Chagas cardiomyopathy pathogenesis. We discuss and summarize the available data related to pathology, pathogenesis, diagnosis, and treatment of reinfections. […] Reinfections influence the genetic and regional diversity of T. cruzi, tissue tropism, modulation of the hosts immune system response, clinical manifestations, the risk for congenital infections, differences in diagnostics performances, response to antiparasitic therapy, and the natural history of the disease. […] Evidence has shown that higher anti-T. cruzi antibodies are correlated with an increased rate of cardiomyopathy and death, suggesting that a higher parasite exposure related to reinfections may lead to worse outcomes. […] Based on the existing literature, reinfections may play a role in developing and exacerbating chronic Chagas cardiomyopathy and are linked to worse outcomes.

• #64 33 Hypertrophic cardiomyopathy: pathogenesis, therapies and disease modulation | Heart Asia

  https://heartasia.bmj.com/content/11/Suppl_1/A14

  Hypertrophic cardiomyopathy (HCM) is a prevalent heritable cardiac disorder, characterised by unexplained left ventricular hypertrophy (LVH) with the triad of myocyte hypertrophy, disarray, and interstitial fibrosis. […] Such pathological hallmarks impact diastolic function and contribute to adverse clinical outcomes: arrhythmias, progressive heart failure and sudden cardiac death. […] Multiple genetic studies have identified considerable numbers of HCM-causing mutations in human sarcomere protein genes, and mice engineered to carry such human mutations recapitulated key phenotypes of HCM. […] Studies in HCM mouse models have illustrated the importance of activated transforming growth factor beta (TGF-) pathway in the early development of HCM. […] Treatment with either TGF- neutralising antibodies or with angiotensin II type 1 receptor antagonist, losartan, was shown to retard and prevent HCM development in mouse models. […] Lately, MYK-461, the first allosteric inhibitor of the cardiac myosin adenosine triphosphate (ATPase), has been shown to reduce left ventricular contractility and attenuate HCM development in mouse models of HCM.

• #65 CAMZYOS® (mavacamten) Mechanism of Action | Safety Profile

  https://www.camzyoshcp.com/mechanism-of-action

  An excess of myosin-actin cross-bridges leads to structural changes in the left ventricle. […] The contractility and energy consumption of the heart are increased. […] The hearts ability to relax is impaired. […] Ultimately, the left ventricular wall thickens, resulting in a blockage or reduced blood flow. […] CAMZYOS is an allosteric and reversible inhibitor selective for cardiac myosin that helps to modulate the number of myosin heads in the off state. This reduces the number of myosin-actin cross-bridges that form. […] Reduced cardiac contractility. […] Reduced dynamic LVOT obstruction. […] Improved cardiac filling pressures. […] Improved energy consumption.

• #66 Chemotherapy Induced Cardiomyopathy: Pathogenesis, Monitoring and Management | Shakir | Journal of Clinical Medicine Research

  https://www.jocmr.org/index.php/JOCMR/article/view/24/0

  The risk for such effects depends upon: cumulative dose, rate of drug administration, mediastinal radiation, advanced age, younger age, female gender, pre-existing heart disease and hypertension. […] Serial measurements of LVEF and fractional shortening are the most common indices monitored to assess left ventricular systolic function and cardiotoxicity. […] Angiotensin-converting enzyme (ACE) inhibitors (ACEIs) have been shown to slow the progression of left ventricular dysfunction in several different clinical settings, including anthracycline-induced cardiomyopathy.

• #67 Nuevocor draws $45M series B for gene therapy in rare heart disease | BioWorld

  https://www.bioworld.com/articles/720049-nuevocor-draws-45m-series-b-for-gene-therapy-in-rare-heart-disease

  Nuevocor Pte. Ltd. has closed a $45 million series B, enabling it to move lead gene therapy NVC-001 into the clinic in the treatment of an inherited form of cardiomyopathy.

• #68 Linda Marbán, PhD, on the Future of Capricor’s Cardiomyopathy Cell Therapy Deramiocel

  https://www.cgtlive.com/view/marban-future-capricor-cardiomyopathy-cell-therapy-deramiocel

  Many people think okay, this is a mutation and so we just have to fix the mutation and then we fix the diseasegene therapy, yay, done, out the door. Not so. Until this disease can be fixed intrauterine where every single cell that the person is born with is normal, they will always have the sequelae associated with the disease. […] Marbn pointed out that although currently approved and investigational gene therapy approaches aim to correct the root mutation causing DMD, these approaches can’t fully eliminate the disease’s long-term effects like inflammation and fibrosis. In fact, patients with DMD will always experience sequelae until a method is developed that can correct the mutation in every cell in utero. As such, Deramiocel can serve as an adjunctive therapy to help address these sequelae in patients who have received genetic treatments for DMD. Furthermore, although Deramiocel is currently being developed for DMD cardiomyopathy, Marbn noted that it may eventually be evaluated for other cardiomyopathies such as Becker cardiomyopathy.

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