Choroba peyroniego
Patofizjologia i mechanizm

Choroba Peyroniego to schorzenie tkanki łącznej prącia, charakteryzujące się lokalnym zwłóknieniem osłonki białawej, prowadzącym do tworzenia blaszek włóknistych, które powodują deformacje prącia i zaburzenia erekcji. Etiopatogeneza opiera się na powtarzających się mikrourazach osłonki białawej, które inicjują kaskadę zapalną i nieprawidłowe gojenie ran, z udziałem kluczowych mediatorów takich jak TGF-β1, PDGF, ROS, NF-κB oraz cytokin prozapalnych (IL-1, IL-6, TNF-α). Proces chorobowy przebiega w dwóch fazach: ostrej (zapalnej) i przewlekłej (włóknistej), z charakterystycznym nadmiarem kolagenu typu I i III, zmniejszeniem elastyny oraz często zwapnieniem blaszek (fosforan wapnia). Genetyczne predyspozycje, w tym związki z antygenem HLA-B7, oraz mechanizmy epigenetyczne (np. deacetylazy histonów) wpływają na rozwój choroby. Patogeneza obejmuje złożone interakcje szlaków sygnałowych TGF-β/Smad, WNT/β-katenina, Hedgehog, YAP/TAZ, MAPK, ROCK i PI3K/AKT, które prowadzą do proliferacji miofibroblastów i nadprodukcji macierzy pozakomórkowej.

  1. Patogeneza choroby Peyroniego
    1. Teoria mikrourazu jako inicjator choroby
    2. Predyspozycje genetyczne
    3. Kluczowe szlaki sygnałowe w patogenezie choroby Peyroniego
    4. Inne szlaki sygnałowe i mechanizmy molekularne
    5. Rola miostatyny i innych czynników
    6. Stres oksydacyjny w patogenezie choroby Peyroniego
  2. Fazy rozwoju choroby Peyroniego
    1. Faza ostra (zapalna)
    2. Faza przewlekła (włóknista)
  3. Molekularne mediatory w patogenezie choroby Peyroniego
    1. Rola TGF-β1
    2. Inne cytokiny i mediatory zaangażowane w patogenezę
  4. Zmiany histopatologiczne w chorobie Peyroniego
    1. Zmiany w składzie kolagenu i elastyny
  5. Związek z innymi chorobami fibrotycznymi
  6. Implikacje dla terapii choroby Peyroniego
    1. Obecne podejścia terapeutyczne oparte na patofizjologii
    2. Nowe kierunki terapeutyczne
    3. Kolejne rozdziały

Patogeneza choroby Peyroniego

Choroba Peyroniego (łac. induratio penis plastica, ang. Peyronie’s disease) jest schorzeniem tkanki łącznej charakteryzującym się występowaniem zlokalizowanego zwłóknienia (blaszki) w obrębie osłonki białawej (tunica albuginea) prącia, pokrywającej ciała jamiste. Dokładny mechanizm powstawania tej choroby nie został jeszcze w pełni poznany, jednak w ostatnich latach badania znacznie poszerzyły wiedzę na temat procesów patofizjologicznych leżących u jej podłoża.123

Teoria mikrourazu jako inicjator choroby

Najszerzej akceptowana teoria dotycząca etiopatogenezy choroby Peyroniego zakłada, że głównym czynnikiem inicjującym jest uraz mechaniczny osłonki białawej. Powtarzające się mikrourazy prącia, szczególnie podczas aktywności seksualnej, powodują stres mechaniczny osłonki i mikrouszkodzenia naczyń. Urazy te prowadzą do uszkodzenia mikrokrążenia, co skutkuje wynacieczeniem krwi, odkładaniem się fibryny i następową kaskadą zapalną.123

Uszkodzenie tkanki inicjuje uwięzienie fibryny, powstawanie nacieku pozanaczyniowego i akumulację białek, nadekspresję cytokin, infiltrację przez makrofagi oraz uwalnianie elastazy, która przekształca kolagen w osłonce z typu I w bardziej włóknisty kolagen typu III. Uważa się, że choroba Peyroniego jest efektem nieprawidłowego procesu gojenia się ran w odpowiedzi na stan zapalny ograniczony do wielu warstw osłonki białawej.123

Hipoteza postawiona przez Devine’a i wsp. sugeruje, że choroba Peyroniego jest inicjowana przez powtarzające się mikrourazy prącia podczas stosunku płciowego. Według tej teorii, pierwotnym miejscem urazu jest osłonka biaława, z rozsunięciem warstw wewnętrznej i zewnętrznej, co tworzy środowisko dla rozwoju stanu zapalnego, przerwania włókien elastycznych i gromadzenia się krwi pozanaczyniowej.12

Predyspozycje genetyczne

Warto zauważyć, że nie u wszystkich mężczyzn, którzy doświadczają urazu prącia, rozwija się choroba Peyroniego. Sugeruje to istnienie predyspozycji genetycznych, które mogą czynić niektórych mężczyzn bardziej podatnymi na rozwój tego schorzenia.12

Badania wskazują na potencjalny związek z układem HLA, szczególnie z antygenem HLA-B7, co może implikować genetyczne podłoże etiologii choroby. Obserwuje się również zwiększone ryzyko wystąpienia choroby Peyroniego u krewnych pierwszego stopnia (rodziców, rodzeństwa, dzieci) pacjentów z tym schorzeniem.123

Nieprawidłowa ekspresja genów może być odpowiedzialna za bliznowacenie występujące w chorobie Peyroniego. Geny nieprawidłowo wyrażone w tej chorobie odpowiadają za kodowanie białek, które pomagają w tworzeniu fibroblastów – komórek tworzących tkankę łączną. W wyniku tego produkowanych jest więcej fibroblastów, co może prowadzić do nagromadzenia tkanki bliznowatej.12

Mechanizmy epigenetyczne, obejmujące deacetylazy histonów (HDAC), zostały również powiązane z patogenezą wielu zaburzeń fibrotycznych oraz odgrywają znaczącą rolę w chorobie Peyroniego, wpływając na stopień zwłóknienia, które może wystąpić po rozpoczęciu choroby.1

Kluczowe szlaki sygnałowe w patogenezie choroby Peyroniego

W patogenezie choroby Peyroniego zaangażowanych jest kilka kluczowych szlaków sygnałowych, z których najważniejszym jest szlak transformującego czynnika wzrostu beta (TGF-β). TGF-β jest przechowywany w formie latentnej w większości normalnych tkanek, ale po urazie tkanki dochodzi do aktywacji latentnych zasobów TGF-β oraz de novo syntezy izoform TGF-β.12

TGF-β1 jest kluczowym czynnikiem aktywacji miofibroblastów i głównym czynnikiem uczestniczącym w zwłóknieniu wszystkich narządów. Nadekspresja TGF-β1 i wyższych poziomów produktów genów pro- i anty-fibrotycznych jest obserwowana w blaszkach choroby Peyroniego.123

TGF-β1 jest rozpuszczalnym czynnikiem wzrostu z nadrodziny TGF-β i wiąże się ze specyficznymi receptorami kinazy serynowo-treoninowej na powierzchni komórki, wywołując aktywację czynników transkrypcyjnych Smad. Skomplikowana sieć sygnalizacyjna czynników transkrypcyjnych Smad reguluje profibrotyczne efekty TGF-β.12

Sygnalizacja TGF-β obejmuje kanoniczną oraz niekanoniczne ścieżki sygnałowe. Szlak sygnałowy TGF-β/SMAD jest regulowany przez inhibicję sprzężenia zwrotnego w celu kontroli homeostazy komórkowej.1

Inne szlaki sygnałowe i mechanizmy molekularne

Oprócz szlaku TGF-β, w patogenezie choroby Peyroniego uczestniczą również inne szlaki sygnałowe. Istnieją dowody na istnienie interakcji (cross-talk) między szlakami TGF-β, WNT/β-katenina, Hedgehog, YAP/TAZ, MAPK, ROCK i PI3K/AKT.123

Profibrotyczny mechanizm sygnalizacji PI3K/AKT indukowanej przez TGF-β1 obejmuje inaktywację NR4A1, który hamuje ekspresję genów profibrotycznych.1

Badania wykazały, że równoległa, nieregulowana aktywność kilku głównych szlaków, z osią sygnalizacyjną TGF-β jako główną, prowadzi do zmienionych interakcji sygnalizacyjnych, co przypuszczalnie skutkuje rozwojem choroby Peyroniego poprzez nieprawidłową naprawę tkanek i zwłóknienie w osłonce białawej.1

Rola miostatyny i innych czynników

Miostatyna, znana również jako GDF-8, jest członkiem rodziny TGF-β. Nadekspresja miostatyny została stwierdzona w większości blaszek choroby Peyroniego. Indukuje ona tworzenie nowych blaszek oraz zagęszcza już istniejące blaszki utworzone przez TGF-β1.12

W patogenezie choroby Peyroniego ważną rolę odgrywa również regulacja syntezy kolagenu przez wiele endogennych i egzogennych peptydów. Zahamowanie i brak kolagenaz przyczyniają się do procesu choroby Peyroniego, podczas gdy iNOS, metaloproteinazy macierzy (MMP)-2 i -9, dekoryna i tymozyny są aktywnymi mechanizmami obronnymi przeciwko chorobie.12

Nierównowaga między metaloproteinazą macierzy (MMP), która usuwa włókna kolagenowe, a jej tkankowym inhibitorem metaloproteinazy (TIMP) w miofibroblastach, wraz z unikaniem apoptozy, są uważane za kluczowe czynniki w rozwoju chorób fibrotycznych.12

Stres oksydacyjny w patogenezie choroby Peyroniego

Badania konsekwentnie wykazały, że stres oksydacyjny jest kluczowym czynnikiem w chorobie Peyroniego, schorzeniu charakteryzującym się przewlekłym stanem zapalnym w ciałach jamistych prącia.12

Zwiększony stres oksydacyjny obserwuje się w procesie włóknienia oraz w zaburzeniach tkanki łącznej w przewlekłych stanach chorobowych wątroby, płuc i układu nerwowego. Ważnymi czynnikami w patogenezie choroby Peyroniego jest regulacja syntezy kolagenu przez wiele czynników endogennych i egzogennych, szczególnie tych, które wytwarzają wolne rodniki tlenowe.12

Produkcja reaktywnych form tlenu (ROS) wywołuje aktywację NF-κB, który kontroluje transkrypcję DNA i specyficznie reguluje ekspresję genów takich jak TGF-β1, bFGF, fibryna, kolagen i indukowana syntaza tlenku azotu (i-NOS), wśród innych.1

Fazy rozwoju choroby Peyroniego

Choroba Peyroniego rozwija się w dwóch fazach: ostrej (zapalnej) i przewlekłej (włóknistej). Zrozumienie tych faz jest kluczowe dla właściwego postępowania terapeutycznego.12

Faza ostra (zapalna)

Podczas fazy ostrej mikrourazy prowadzą do uszkodzenia śródbłonka, odkładania fibryny i migracji komórek immunologicznych do osłonki białawej. Proliferacja fibroblastów i różnicowanie miofibroblastów są promowane przez cytokiny takie jak TGF-β1, PDGF (płytkopochodny czynnik wzrostu) i ROS (reaktywne formy tlenu).12

Napływ leukocytów i makrofagów, jako odpowiedź zapalna, postępuje przez przepływ tętniczy, co prowadzi do produkcji dużej ilości cytokin. Ta faza charakteryzuje się formowaniem blaszki, która jest tkliwa przy palpacji z powodu aktywnego miejscowego procesu zapalnego. Rozciąganie blaszek, jak fizjologicznie występuje podczas erekcji, wywołuje wyraźny ból.12

W odpowiedzi na uraz, patogeneza blaszek choroby Peyroniego jest uważana za efekt kilku potencjalnych czynników. Są to m.in. nieodpowiednia odpowiedź włóknista poprzez nadprodukcję kolagenu i zmiany typu kolagenu odkładanego w osłonce, nadprodukcja cytokin indukujących włóknienie, zmiany w odporności komórkowej zależnej od limfocytów T oraz asocjacje z układem HLA, lub niezdolność do degradacji i usunięcia fibryny z osłonki białawej.1

Faza przewlekła (włóknista)

W fazie przewlekłej (włóknistej) zmienione procesy naprawcze z pierwszej fazy prowadzą do tworzenia gęstych włóknistych blaszek, które mogą również postępować do zwapnienia, stabilizując lub pogarszając krzywiznę prącia.12

Stan zapalny jest zmniejszony, ale włóknista blaszka jest zachowana, a częściowe zwapnienie występuje w większości przypadków. Powoduje to strukturalne zniekształcenie tkanki prącia i brak elastyczności, co utrudnia normalny wzrost podczas erekcji. Intensywne zwapnienie i włóknienie zaburzają normalną hemodynamikę i elastyczność prącia, co zwykle powoduje przeciek żylny i zaburzenia erekcji.12

Faza przewlekła rozpoczyna się, gdy proces zapalny ostatecznie ustępuje, zwykle około 3 do 9 miesięcy od początku choroby. Na tym etapie ból generalnie ustępuje, a deformacja stabilizuje się.1

Molekularne mediatory w patogenezie choroby Peyroniego

Najważniejszymi mediatorami biologicznymi w patogenezie choroby Peyroniego są: reaktywne formy tlenu (ROS), reaktywne formy azotu (RNS), czynnik jądrowy kappa B (NF-κB), transformujący czynnik wzrostu beta-1 (TGF-β1), płytkopochodny czynnik wzrostu (PDGF), interleukina-1 (IL-1), podstawowy czynnik wzrostu fibroblastów (bFGF), inhibitor aktywatora plazminogenu-1 (PAI-1) oraz czynnik martwicy nowotworów alfa (TNF-α).12

Rola TGF-β1

TGF-β1 jest cytokiną wydzielaną przez makrofagi, płytki krwi, limfocyty T i neutrofile. TGF-β1 wykonuje następujące działania:

  • Przyciąga neutrofile, monocyty, limfocyty i fibroblasty1
  • Promuje wzrost fibroblastów i ich przekształcanie w miofibroblasty12
  • Indukuje produkcję kolagenu przez fibroblasty1
  • Stymuluje syntezę i odkładanie kolagenu1
  • Promuje osteogenezę w blaszce choroby Peyroniego12
  • Zwiększa produkcję tkankowych inhibitorów metaloproteinaz macierzy (TIMP-1)1

Zwapnienie blaszki, składające się głównie z fosforanu wapnia, występuje z powodu zwiększonej aktywności TGF-β1, która zwiększa osteogenezę i zwiększa ekspresję pleiotrofiny, osteogennego czynnika wzrostu, który stymuluje aktywność fibroblastów i osteoblastów.1

Inne cytokiny i mediatory zaangażowane w patogenezę

W patogenezie choroby Peyroniego uczestniczą również inne cytokiny i mediatory, w tym:

  • Inhibitor aktywatora plazminogenu typu 1 (PAI-1): Przyczynia się do fibrynogenezy i włóknienia12
  • Płytkopochodny czynnik wzrostu (PDGF): Promuje proliferację fibroblastów i różnicowanie miofibroblastów123
  • Interleukina-1 (IL-1) i interleukina-6 (IL-6): Zaangażowane w reakcję zapalną i fibrogenezę123
  • Podstawowy czynnik wzrostu fibroblastów (bFGF): Stymuluje proliferację fibroblastów12
  • NF-κB: Kontroluje transkrypcję DNA i reguluje ekspresję genów zaangażowanych w procesy zapalne i fibrotyczne123

Zmiany histopatologiczne w chorobie Peyroniego

Histologicznie blaszki choroby Peyroniego charakteryzują się dezorganizacją kolagenu związaną ze zmniejszeniem gęstości elastyny. Początkowa odpowiedź zapalna charakteryzuje się przewlekłym naciekiem limfocytowym i plazmocytowym osłonki białawej.123

Jeśli tworzenie się tkanki bliznowatej i odkładanie się macierzy pozakomórkowej przewyższa degradację kolagenu i macierzy, wówczas zwiększone ilości kolagenu odkładają się w osłonce białawej, co prowadzi do włóknienia i tworzenia blaszki.1

Miofibroblasty nadekspresjonują kolagen typu I i białka macierzy pozakomórkowej, prowadząc do tworzenia blaszki. W przewlekłej postaci stan zapalny jest zmniejszony, ale włóknista blaszka jest zachowana, a częściowe zwapnienie występuje w większości przypadków.1

Zmiany w składzie kolagenu i elastyny

Choroba Peyroniego charakteryzuje się miejscowymi zmianami w składzie kolagenu i włókien elastycznych osłonki białawej. Formowanie się włóknistych blaszek zmienia anatomię prącia i może powodować różne stopnie zgięcia, zwężenia lub skrócenia prącia.1

Podczas procesu gojenia po urazie prącia tworzy się tkanka bliznowata. Może to prowadzić do guzka, który możesz wyczuć, lub krzywizny prącia. W chorobie Peyroniego, gdy prącie staje się wzwiedziane, obszar z tkanką bliznowatą nie rozciąga się. W rezultacie prącie wygina się lub przechodzi inne zmiany.1

Blaszka prąciowa lub tkanka bliznowata może zakłócać sposób, w jaki prącie przechowuje odpowiednią ilość krwi podczas erekcji. Prowadzi to do niezdolności uzyskania lub utrzymania erekcji, która jest wystarczająco twarda, aby odbyć stosunek płciowy.1

Związek z innymi chorobami fibrotycznymi

Choroba Peyroniego jest zaburzeniem gojenia ran, podobnym do keloidów, blizn przerostowych lub przykurczów Dupuytrena, z którymi może współwystępować. Gęste blaszki identyfikowane w chorobie Peyroniego są wynikiem nierównowagi między włóknieniem a fibrynolizą.1

Uważa się, że istnieje związek między chorobą Peyroniego a przykurczem Dupuytrena. Mechanizmy leżące u podłoża choroby Peyroniego wydają się nie być specyficzne tylko dla tego schorzenia, biorąc pod uwagę znaczne nakładanie się patologii, występowania i epidemiologii między chorobą Peyroniego a innymi zlokalizowanymi schorzeniami włóknistymi, takimi jak choroba Dupuytrena i choroba Ledderhose.12

Obecnie wiedza na temat szlaków molekularnych zapalenia i włóknienia wciąż nie jest wystarczająco jasna. Uraz prącia nie zawsze prowadzi do choroby Peyroniego, a pacjenci z chorobą Peyroniego nie zawsze mają historię urazu prącia. Ten fakt, wraz z nierównym występowaniem w różnych grupach etnicznych i dostrzeżonymi korelacjami z innymi chorobami fibroproliferacyjnymi, skłonił do badań genetycznych, głównie w dziedzinach antygenów grupy HLA, autoimmunologii, polimorfizmów pojedynczych nukleotydów i aberracji kariotypu.1

Implikacje dla terapii choroby Peyroniego

Zrozumienie mechanizmów molekularnych patogenezy choroby Peyroniego ujawniło obiecujące cele molekularne dla terapii przeciwfibrotycznych. Aby określić bardziej skuteczną opcję leczenia, należy najpierw w pełni zrozumieć kompletną komórkową podstawę patofizjologii tej choroby.1

Zidentyfikowano konkretne MMPs, TIMPs i cytokiny, a interwencje ukierunkowane na nie są obecnie w trakcie opracowywania. Lepsze zrozumienie zarówno związanych mechanizmów molekularnych, jak i wieloczynnikowych czynników związanych z patogenezą choroby Peyroniego będzie miało duży wpływ na opcje leczenia, a także strategie zapobiegania.12

W kontekście korzyści terapeutycznych wynikających ze zrozumienia mechanizmów patofizjologicznych choroby Peyroniego, udowodniono, że nadekspresja TGF-β i aktywacja czynników transkrypcyjnych Smad są kluczowe w patogenezie choroby Peyroniego.1

Obecne podejścia terapeutyczne oparte na patofizjologii

Badania nad patofizjologią choroby Peyroniego doprowadziły do rozwoju kilku podejść terapeutycznych:

  • Kolagenaza Clostridium histolyticum (CCH): Jest chromatograficznie oczyszczonym enzymem bakteryjnym, który selektywnie atakuje kolagen, główny składnik blaszki choroby Peyroniego. Rozkłada ona tkankę bliznowatą i zmniejsza rozmiar blaszki i krzywiznę.123
  • Pentoksyfilina (PTX): Ma kilka mechanizmów działania, w tym antyoksydacyjne, antyfibrotyczne, przeciwzapalne i wazorelaksacyjne. Badania wykazały, że PTX jest w stanie zmniejszyć objawy choroby, w tym krzywiznę, ból i zaburzenia erekcji.12
  • Poaminobenzoesan potasu (Potaba): Uważa się, że ma działanie antyfibrotyczne poprzez zmniejszanie stężenia serotoniny, która przyczynia się do fibrynogenezy.1
  • Tamoksyfen: Hamuje uwalnianie transformującego czynnika wzrostu alfa i beta z ludzkich fibroblastów, co prowadzi do zmniejszenia odpowiedzi zapalnej w zmianach i zmniejszenia rozmiaru blaszki poprzez hamowanie angiogenezy i fibrynogenezy.1
  • Acetylo-L-karnityna: Hipotezuje się, że zapobiega proliferacji fibroblastów i kolagenogenezie poprzez zmniejszenie wolnych rodników i wewnątrzkomórkowego stężenia wapnia.1
  • Inhibitory PDE5: Spekuluje się, że zapobiegają rozwojowi blaszki i zmniejszają jej rozmiar poprzez utrzymanie wysokiego poziomu cyklicznego monofosforanu guanozyny w tkance docelowej, co ma działanie przeciwfibrotyczne.1

Nowe kierunki terapeutyczne

Wysiłki naukowe powinny być ukierunkowane na wyjaśnienie biologicznych mechanizmów choroby Peyroniego. Obecne zrozumienie patogenezy sugeruje zaangażowanie czynników zapalnych, cytokin, czynników wzrostu i innych czynników molekularnych zaangażowanych w uraz tkanki, włóknienie i nieprawidłowe gojenie ran.1

Trwające badania naukowe, które definiują patofizjologię molekularną tego zaburzenia, mogą sugerować miejsca molekularne, które mogą być celem terapeutycznym. W uznaniu prawdopodobnego uwarunkowania genetycznego lub podatności na chorobę Peyroniego u wielu osób, należy zintensyfikować badania naukowe w odkrywaniu czynników genetycznych związanych z tym stanem.1

Prace badawcze obejmujące profile ekspresji genów i opisujące mutacje genów białek komórkowych zaangażowanych w włóknienie tkanek i zwapnienie blaszek są najbardziej istotne. Takie prace mogą również prowadzić do ustanowienia biomarkerów, które można zastosować do oceny choroby i związanych z nią procedur diagnostycznych (np. czynniki predykcyjne progresji, spontanicznego ustąpienia, a być może odpowiedzi na leczenie).1

Terapia genowa, terapia komórkami macierzystymi i medycyna regeneracyjna mogą być również rozważane jako mające potencjalną przyszłą rolę w tym schorzeniu. W kontekście choroby Peyroniego, terapia komórkami macierzystymi ma na celu wykorzystanie tego potencjału regeneracyjnego do naprawy uszkodzonej tkanki w prąciu.12

Mechanizm działania terapii komórkami macierzystymi w chorobie Peyroniego obejmuje kilka kluczowych procesów, które przyczyniają się do naprawy i regeneracji tkanek w prąciu:

  • Komórki macierzyste posiadają właściwości przeciwzapalne, które pomagają zmniejszyć stan zapalny w tkance prącia dotkniętej chorobą Peyroniego.1
  • Komórki macierzyste mają unikalną zdolność do różnicowania się w różne typy komórek, w tym komórki mięśni gładkich, komórki śródbłonka i fibroblasty, które są niezbędne do naprawy i regeneracji tkanek.1
  • Komórki macierzyste wydzielają różne czynniki i enzymy, które pomagają przebudować macierz pozakomórkową, rozkładając tkankę bliznowatą i promując syntezę nowej, zdrowej tkanki.1
  • Poprzez zwiększenie przepływu krwi do prącia, komórki macierzyste poprawiają natlenowanie tkanek i dostarczanie składników odżywczych, ułatwiając gojenie i regenerację.1
  • Komórki macierzyste mają właściwości immunomodulacyjne, co oznacza, że mogą modulować odpowiedź immunologiczną i promować tolerancję tkanek.1

Poprzez wstrzyknięcie komórek macierzystych bezpośrednio w dotknięty obszar prącia, celem jest modulowanie stanu zapalnego, zmniejszenie tworzenia się tkanki bliznowatej i potencjalne poprawienie krzywizny prącia, bólu i funkcji erekcyjnej.1

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  1. 09.04.2026
  2. www.leksykon.com.pl

Materiały źródłowe

  • #1 Peyronie Disease – StatPearls – NCBI Bookshelf
    https://www.ncbi.nlm.nih.gov/books/NBK560628/
    Peyronie disease is a wound-healing disorder of the tunica albuginea that results in localized fibrosis or scarring of the tunica albuginea. The abnormal curvature is caused by localized scar tissue in the walls of the corpora; the exact mechanism responsible for forming this fibrotic area remains elusive. […] The exact mechanism of plaque formation is yet to be definitively established; the most generally accepted theory is that the plaque forms as a result of some degree of penile injury or microtrauma, particularly in men who are genetically predisposed to the condition. […] Repetitive minor trauma to the penis causing tunical mechanical stress and microvascular injury are the major contributory factors. […] This trauma damages the microvasculature, resulting in blood extravasation, fibrin deposition, and a subsequent inflammatory cascade, including fibrin trapping, extravascular infiltrate and protein accumulations, overexpression of cytokines, infiltration by macrophages, and the release of elastase, which converts the collagen in the tunica from type 1 to the more fibrous and type III.
  • #1 The pathophysiology of Peyronie’s disease
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4442979/
    To review the contemporary knowledge of the pathophysiology of Peyronies disease (PD). […] Many theories have been proposed to explain the cause of PD, but the true pathogenesis of PD remains an enigma. Identifying particular growth factors and the specific genes responsible for the induction of PD have been the ultimate goal of research over the past several decades. […] The pathogenesis of PD has been explored in animal models, cell cultures and clinical trials, but the results have led to further questions. New research on the aetiology and pathogenesis of PD is needed, and which will hopefully improve the understanding and management for patients with this frustrating disease. […] The pathogenesis remains uncertain and there is still controversy about the best management. […] PD can thus be considered as an aberrant wound-healing process in response to an inflammation constrained within the many layers of the TA.
  • #1 Molecular Mechanisms and Risk Factors Related to the Pathogenesis of Peyronie’s Disease
    https://www.mdpi.com/1422-0067/24/12/10133
    The hypothesis posed by Devine et al. that PD is initiated by repetitive micro-trauma to the penis during intercourse has become widely accepted. […] For affected patients, the primary site of injury is thought to be the TA, with disruption of the inner and outer layers creating a milieu for inflammation, elastic fiber disruption, and extravascular blood accumulation. […] Transforming growth factor-β1 (TGF-β1) is a key factor for myofibroblast activation and a major player in fibrosis in all organs. […] An imbalance between matrix metalloproteinase (MMP), which removes collagen fibers, and its tissue inhibitor of metalloproteinase (TIMP) in myofibroblasts, along with the evasion of apoptosis, are thought to be key factors in the development of fibrotic diseases. […] Based on the latest reported findings, details regarding the mechanisms of fibrotic tissue remodeling and putative functions of each cell type during different stages of PD are presented below.
  • #1 Peyronie Disease: Practice Essentials, Problem, Epidemiology
    https://emedicine.medscape.com/article/456574-overview
    Peyronie disease (PD) is characterized by curvature in the penile shaft that is often preceded by painful erections and accompanied by an area of fibrosis. […] The etiology of PD remains enigmatic. PD has been associated with deficiency in vitamin E, ingestion of beta-blocking agents, and elevations of serotonin levels. PD is associated with Dupuytren contractures and with HLA-B7, implying a genetic link to its etiology. […] More recently, PD has been thought to result from vascular trauma or injury to the penis. The injury may be trivial or involve only microscopic vessels and tissues. This triggers the release of cytokines that activate fibroblast proliferation and produce collagen, the main matrix component of a Peyronie plaque, within the tunica albuginea. […] In PD, the initial inflammatory response is characterized by chronic lymphocytic and plasmacytic infiltration of the tunica albuginea. This may be the result of minor penile trauma, as can happen unnoticed during intercourse.
  • #1 Can Peyronie’s Disease Be Inherited?
    https://www.healthline.com/health/mens-health/peyronies-disease-inherited
    Faulty gene expression might be behind the scarring that happens in Peyronies disease. Genes that are abnormally expressed in this disease are responsible for coding the proteins that help to make fibroblasts cells that form connective tissue. As a result, more fibroblasts are produced, which can lead to the buildup of scar tissue in Peyronies disease. […] Scientists are trying to learn more about the genetic factors involved in Peyronies disease. Genes that are eventually discovered could lead to the development of biomarkers that help doctors diagnose and treat Peyronies more quickly and effectively. […] Though scientists dont know the exact cause of Peyronies disease, they believe a combination of genes and environmental factors are involved. The condition usually happens after an injury to the penis, but genes may make some people more susceptible than others to developing Peyronies after an injury.
  • #1 Epigenetic Profiles of Men With Peyronie’s Disease – American Urological Association
    https://auanews.net/issues/articles/2024/june-extra-2024/epigenetic-profiles-of-men-with-peyronies-disease
    Peyronie’s disease (PD) is a fibrosing disorder with a prevalence of up to 11% in the United States. This evidence supports a pathophysiology centered on a genetic predisposition towards fibrosis in a subset of men, rather than a set of isolated fibrotic conditions brought about by discrete traumatic occurrences. […] Epigenetic regulation involving histone deacetylases (HDAC) has already been implicated in the pathogenesis of multiple fibrotic disorders of the kidneys, bladder, lungs, heart, and liver and has subsequently been found to play a significant role in PD, including the extent of fibrosis that may occur after disease onset. […] This suggests that variations in methylation and subsequent gene expression without overt genetic defects may predispose men to the condition and can be targets for treatment.
  • #1 Molecular Mechanisms and Risk Factors Related to the Pathogenesis of Peyronie’s Disease
    https://www.mdpi.com/1422-0067/24/12/10133
    TGF-β is stored in a latent form in most normal tissues, while upon tissue injury, de novo synthesis of TGF-β isoforms and latent stores of TGF-β are activated. […] Indeed, activation of TGF-β signaling through the subtunical injection of TGF-β1 in rat and rabbit models has been demonstrated to induce PD-like plaque formation in the penis. […] TGF-β signaling includes SMAD-mediated canonical and non-canonical TGF-β signaling pathways. […] The TGF-β/SMAD signaling pathway is regulated by feedback inhibition to control cellular homeostasis. […] These observations were supported by other later studies. […] The profibrotic mechanism of TGF-β1-induced PI3K/AKT signaling involves the inactivation of NR4A1, which inhibits the expression of profibrotic genes. […] Therefore, parallel non-regulated activity of several core pathways, with TGF-β signaling pathway as the main axis, that simultaneously leads to altered signaling crosstalk can conceivably result in the development of PD via aberrant tissue repair and fibrosis in TA tissues.
  • #1 Peyronie’s disease: a literature review on epidemiology, genetics, pathophysiology, diagnosis and work-up – Al-Thakafi – Translational Andrology and Urology
    https://tau.amegroups.org/article/view/10408/html
    The influx of leukocytes and macrophages, as an inflammatory response, continues via arterial flow, resulting in production of a large amount of cytokines. […] The above theories attempt to explain that PD is caused due to aberrant wound-healing process, in response to trauma within the layers of tunica albuginea. […] Fibrogenesis in many chronic hepatic, pulmonary, and neuronal degeneration diseases is caused due to oxidative stress. […] Increased expression of TGF-1 and higher levels of pro-and anti-fibrotic gene products could be observed in PD. […] TGF-1 is a soluble growth factor of the TGF- superfamily, and binds to specific serine/threonine kinase receptors on cell surface, triggering the activation of Smad transcription factors. […] A complicated signaling network of Smad transcription factors regulates the profibrotic effects of TGF-.
  • #1 Peyronie Disease – StatPearls – NCBI Bookshelf
    https://www.ncbi.nlm.nih.gov/books/NBK560628/
    Wound healing is delayed and becomes unregulated due to the prolonged inflammation. The enhancement of fibrous tissue production is mediated by TGF-1, PAI-1, PDGF, IL-1, and IL-6. […] These effects collectively result in an inflammatory cascade that promotes localized fibrosis and plaque formation over normal wound consolidation. […] Other theories have been suggested to explain the formation of the plaques, including microtrauma, microvasculature injury, chromosomal instability of fibroblasts involved in plaque formation, aberrations in the inducible nitric oxide pathways, and patient HLA subtype. […] There is evidence that crosstalk may be involved between TGF-, WNT/-catenin, Hedgehog, YAP/TAZ, MAPK, ROCK, and PI3K/AKT signaling pathways. […] Plaque calcification, primarily composed of calcium phosphate, occurs due to increased TGF-1 activity, which enhances osteogenesis and upregulates pleiotrophin, an osteogenic growth factor that stimulates fibroblast and osteoblast activity.
  • #1 The pathophysiology of Peyronie’s disease
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4442979/
    TGF- has recently received attention as a cytokine influencing the deposition of extracellular matrix, and inducing fibrosis in the TA. […] The overexpression of myostatin, a member of TGF- family, has been found in PD plaques, and it induced new plaque when induced, and condensed the plaque already formed by TGF- 1. […] The inhibition and lack of collagenases contribute to the PD process, while iNOS, matrix metalloproteinases (MMP)-2 and -9, decorin and thymosins are the active defence mechanisms against the disease. […] The persistence of myofibroblasts which are removed by apoptosis was investigated in a recent study in which the expressions of apoptotic genes were investigated. […] In relation to the therapeutic benefits of understanding the pathophysiological mechanisms of PD, Jang et al. reported that the overexpression of TGF- and activation of Smad transcriptional factors are known to be crucial in the pathogenesis of PD.
  • #1 Oxidative Mechanism of Peyronie’s Disease and Effectiveness of Pentoxifylline in the Therapeutic Management: A Narrative Review
    https://www.mdpi.com/2076-3921/14/2/208
    Peyronie’s disease (PD) is a chronic disease characterized by the development of fibrous tissue in the tunica albuginea of the penile corpora cavernosa that causes penile deformity. […] The precise cause of PD is not completely understood, but it is generally believed to be initiated by a specific injury in the affected area. […] Research has consistently shown that oxidative stress (OS) is a key player in PD. […] The exact cause of PD is not fully understood, but it is commonly thought to be triggered by a specific injury in the affected area. […] Although PD can be triggered by coital sexual trauma or injury, in 70% of cases, no specific cause is found, and patients do not remember the traumatic event. […] Following an injury, fibrin is deposited, and a hematoma forms. […] However, in individuals with a genetic predisposition, the hematoma that forms triggers the activation of inflammatory cells and pro-inflammatory cytokines, leading to the subsequent formation of an area of chronic inflammatory tissue that inevitably progresses to fibrosis (plaque).
  • #1 The pathophysiology of Peyronie’s disease
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4442979/
    The initiation of the disease is accepted as the extravasation of fibrinogen, converted to fibrin with the aid of thrombin, in the intralaminar space in the TA before the inflammation and fibrosis of both the plaque and normal-looking TA. […] Devine and Horton hypothesised that PD is caused by an abnormal fibrotic reaction to minimal trauma. […] These findings support the notion that entrapment of inflammatory cells and the deposition of extracellular matrix in the multi-layered structure of the TA is the key factor in inducing PD. […] There is reportedly an increase in oxidative stress in fibrogenesis, and an increase in connective tissue disorders in chronic disease states of hepatic, pulmonary and nervous system tissue degeneration. […] Important factors in the pathogenesis of PD include the regulation of collagen synthesis by many endogenous and exogenous factors, particularly those that produce oxygen-free radicals.
  • #1 Oxidative Mechanism of Peyronie’s Disease and Effectiveness of Pentoxifylline in the Therapeutic Management: A Narrative Review
    https://www.mdpi.com/2076-3921/14/2/208
    The production of ROS triggers the activation of NF-κB, which controls DNA transcription and specifically regulates the expression of genes such as TGF-β1, bFGF, fibrin, collagen, and inducible nitric oxide synthase (i-NOS), among others. […] TGF-β1 is a cytokine secreted by macrophages, platelets, T lymphocytes, and neutrophils. […] TGF-β1 carries out the following actions: It attracts neutrophils, monocytes, lymphocytes, and fibroblasts; promotes fibroblast growth and their transformation into myofibroblasts; induces collagen production by fibroblasts; stimulates collagen synthesis and deposition; promotes osteogenesis in the PD plaque; and enhances the production of tissue inhibitors of matrix metalloproteinases (TIMP-1). […] PTX has several mechanisms of action, including antioxidant, antifibrotic, anti-inflammatory, and vasorelaxant.
  • #1 Peyronie’s disease – Wikipedia
    https://en.wikipedia.org/wiki/Peyronie%27s_disease
    Peyronie’s disease develops in two phases: the acute (inflammatory) and chronic (fibrotic) phase. During the acute phase, microtrauma induces damage to the endothelium, fibrin deposition, and immigration of immune cells into the tunica albuginea. Fibroblast proliferation and myofibroblast differentiation are promoted by cytokines like TGF-1, PDGF (platelet-derived growth factor), and ROS (reactive oxygen species). Myofibroblasts overexpress type I collagen and extracellular matrix proteins, leading to plaque formation. In the chronic presentation, inflammation is reduced, but the fibrotic plaque is preserved, and partial calcification occurs in most cases. This causes structural deformity of the penile tissue and inelasticity that impedes normal growth during an erection. Intense calcification and fibrosis impair normal hemodynamics and penile elasticity of the penis, which usually causes venous leakage and erectile failure.
  • #1 The Clinical and Psychosocial Impact of Peyronie’s Disease
    https://www.ajmc.com/view/a449_13mar_peyronies_levine_s55
    Peyronies disease (PD) is characterized by the formation of palpable fibrotic tissue in the tunica albuginea of the penis. […] The most widely accepted etiology is thought to involve a repetitive minor trauma to the tunica albuginea during erection with subsequent abnormal wound healing. […] In response to trauma, the pathogenesis of PD plaques is thought to occur via a number of potential contributors. […] These include an inappropriate fibrotic response via an overproduction of collagen and alterations in the type of collagen deposited in the tunica, an overproduction of cytokines that induce fibrosis, alterations in T-cell-mediated immunity and human leukocyte antigen system associations, or failure to degrade and clear fibrin from the tunica albuginea. […] The exact cascade of events leading to PD remains unclear.
  • #1 What causes Peyronies’s Disease?
    https://www.andrology.co.uk/peyronies-disease/what-causes-peyronies-disease
    At present, the actual mechanism causing Peyronies disease is still unknown. […] It is suspected that this condition occurs in the genetically predisposed patient following a trauma to the erect penis. Possibly patients with Peyronies Disease present an imbalance in the factors promoting the healing process after a trauma and this leads to excessive local tissue proliferation following a trauma. Typically Peyronies Disease presents an initial acute and a chronic phase. The acute phase is characterized by the formation of the plaque, which is tender at palpation as there is an active local inflammatory process. During this phase, stretching of the plaques, as physiologically occurs during erections, elicits vivid pain. […] The chronic phase starts when the inflammatory process eventually settles, usually around 3 to 9 months from the onset of the condition. At this stage the pain generally settles and the deformity stabilizes.
  • #1 Oxidative Mechanism of Peyronie’s Disease and Effectiveness of Pentoxifylline in the Therapeutic Management: A Narrative Review
    https://www.mdpi.com/2076-3921/14/2/208
    Histologically, the Peyronie’s plaques are characterized by a disorganization of collagen associated with a reduction in the density of elastin. […] Numerous studies have demonstrated that oxidative stress (OS) is a crucial factor in all types of inflammatory processes, whether they are acute or chronic. […] Research has consistently shown that OS is a key player in PD, a condition characterized by chronic inflammation in the penile corpora cavernosa. […] The most important biological mediators in the pathogenesis of PD are as follows: reactive oxygen species (ROS), reactive nitrogen species (RNS), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), transforming growth factor beta-1 (TGF-β1), platelet-derived growth factor (PDGF), interleukin-1 (IL-1), basic fibroblast growth factor (bFGF), plasminogen activator inhibitor-1 (PAI-1), and tumor necrosis factor-alpha (TNF-α).
  • #1 Peyronie Disease: Practice Essentials, Problem, Epidemiology
    https://emedicine.medscape.com/article/456574-overview
    If scar tissue formation and extracellular matrix deposition exceed collagen and matrix degradation, then increased collagen is deposited in the tunica albuginea, resulting in fibrosis and plaque formation. […] Transforming growth factor-beta (TGF-beta) is a cytokine involved in tissue repair and scar formation. […] The authors were able to derive and confirm several conclusions as to the role of microtrauma, cytokines, myofibroblasts, and oxidative stress in the initiation and progression of plaque.
  • #1
    https://link.springer.com/article/10.1007/s11934-000-0010-8
    Peyronies disease is an idiopathic, localized connective tissue disorder of the penis that involves the tunica albuginea of the corpus cavernosum and the adjacent areolar space. […] Peyronies disease is characterized by local changes in the collagen and elastic fiber composition of the tunica albuginea. […] The formation of fibrotic plaques alters penile anatomy and can cause different degrees of bending, narrowing, or shortening of the penis. […] Moreover, a significant number of men with Peyronies disease develop erectile dysfunction. […] Penile blood flow studies in many patients with Peyronies disease suggest a strong association with veno-occlusive dysfunction. […] Although long recognized as an important clinical entity of the male genitalia, the etiology of this disease has remained poorly understood. […] The following review focuses on recent research on the pathophysiology of Peyronies disease.
  • #1 Peyronie disease – Symptoms and causes – Mayo Clinic
    https://www.mayoclinic.org/diseases-conditions/peyronies-disease/symptoms-causes/syc-20353468
    Peyronie disease is a condition in which fibrous scar tissue forms in the deeper tissues under the skin of the penis. This causes curved, painful erections. […] The exact cause of Peyronie disease isn’t clear. But various factors seem to be involved. […] It’s thought Peyronie disease most often results from repeated injury to the penis during vigorous sex. But the penis also could be damaged during athletic activities or accidents. Many people with Peyronie disease can’t recall a specific injury that led to their symptoms. […] During the healing process after injury to the penis, scar tissue forms. This can lead to a lump you can feel or to a curve in the penis. […] In Peyronie disease, when the penis becomes erect, the area with the scar tissue doesn’t stretch. As a result, the penis bends or goes through other changes. This can be painful. […] In most people, Peyronie disease symptoms come on slowly and don’t seem to be linked with an injury. Researchers are looking into whether Peyronie disease might be tied to a genetic trait or certain health conditions.
  • #1 Peyronie’s Disease: Causes, Symptoms, Diagnosis & Treatment
    https://my.clevelandclinic.org/health/diseases/10044-peyronies-disease
    The penile plaque or scar tissue can interfere with how your penis stores an adequate amount of blood during erection. This results in an inability to get or maintain an erection thats hard enough to have intercourse. […] Severe Peyronies disease can shorten your penis. […] The amount of length that you lose depends on how severe your penile curve is. Severe Peyronies disease can decrease the length of your penis from 0.5 cm (about 50 sheets of paper stacked on top of each other) to 1.5 cm (about 150 sheets of paper). […] Healthcare providers only recommend surgery if you have severe Peyronies disease that makes it difficult or impossible to have sex. You should only have surgery if youre in the stable or chronic phase of Peyronies disease, in which the scarring and curvature no longer progress and you havent had any pain for between six and 12 months. […] When scar tissue builds up in your penis, it can cause it to bend, curve or even get shorter.
  • #1 Understanding the cellular basis and pathophysiology of Peyronie’s disease to optimize treatment for erectile dysfunction – Campbell – Translational Andrology and Urology
    https://tau.amegroups.org/article/view/12563/html
    The devastating sexual and psychological impact PD has on patients necessitates improved treatment and prevention strategies. […] Our current therapies frequently do not meet expectations and therefore to further develop new strategies, we need a complete understanding of the precise cellular and pathophysiologic processes of PD and gather knowledge of how we can intervene at a molecular level. […] PD is a wound-healing disorder, similar to keloids, hypertrophic scars, or Dupuytrens contractures, all of which may be coinciding findings. […] The dense plaques identified in PD are a result of an imbalance of fibrosis and fibrinolysis. […] Fibrosis is the result of chronic inflammation which can be induced by persistent infections, autoimmune reactions, allergic responses, chemical insults, radiation, and tissue injuries.
  • #1 Peyronie’s Disease | Patient Care
    https://weillcornell.org/services/urology/male-infertility-and-sexual-medicine/conditions-we-treat/peyronies-disease
    Peyronie’s disease is characterized by a localized scarring of the tunica albuginea of the penis. […] Many theories have been proposed for the pathogenesis of Peyronie’s disease, including auto-immune factors, excess production of chemicals (known as cytokines) in the tissue of the penis and abnormalities of cell behavior. […] It is also believed that there is an association between Peyronie’s disease and Dupuytren’s disease (aka Dupuytren’s contracture). […] Another possible cause of Peyronie’s disease was believed to be hypogonadism, or low testosterone, although this has not held true.
  • #1 Peyronie’s Disease | SpringerLink
    https://link.springer.com/chapter/10.1007/978-3-031-11701-5_6
    The altered repair processes of the first phase result in the formation of dense fibrotic plaques which may also progress to calcification, stabilizing, or worsening the penile curvature. […] Current knowledge on the matter of molecular pathways of inflammation and fibrosis still seems not enough clear. Indeed, penile trauma does not always result in PD, and PD patients do not always have a history of penile trauma. This fact, along with an uneven prevalence across ethnicities and the noted correlations with other fibroproliferative diseases, has prompted research in genetics, mainly in the fields of HLA group antigens, autoimmunity, single nucleotide polymorphisms and karyotype aberrations. Nevertheless, results in this field have been inconclusive.
  • #1 Understanding the cellular basis and pathophysiology of Peyronie’s disease to optimize treatment for erectile dysfunction – Campbell – Translational Andrology and Urology
    https://tau.amegroups.org/article/view/12563/html
    It does appear that this genetic predisposition is localized to the TA rather than a systemic alteration given the lack of associated disease manifestations in PD patients. […] Further assessment is possible with DNA-based chip arrays, and the results from the PD plaques are encouraging. […] Advances in our understanding of molecular mechanisms of PD pathogenesis have revealed promising molecular targets for anti-fibrotic treatments. […] To determine a more effective treatment option, one must first fully understand the complete cellular basis to the pathophysiology of this disease. […] Understanding the early causative factors of this disease will allow us to intervene earlier and prevent long-term complications and worsening ED. […] The precise mechanisms are still under investigation, although we are getting close. […] Specific MMPs, TIMPs, and cytokines have been identified and interventions that target these are currently under development.
  • #1 EAU Guidelines on Sexual and Reproductive Health – Uroweb
    https://uroweb.org/guidelines/sexual-and-reproductive-health/chapter/penile-curvature
    The rationale for intralesional use of channel antagonists in patients with PD is based on in vitro research. […] Collagenase of Clostridium histolyticum (CCH) is a chromatographically purified bacterial enzyme that selectively targets collagen, the primary component of the PD plaque. […] Penile prosthesis (PP) implantation is typically reserved for the treatment of PD in patients with concomitant ED not responding to conventional medical therapy (PDE5I or intracavernous injections of vasoactive agents).
  • #1 :: WJMH :: World Journal of Men’s Health
    https://wjmh.org/DOIx.php?id=10.5534/wjmh.2016.34.1.40
    Peyronie’s disease is a localized connective tissue disorder that involves tunica albuginea of the penis. […] Potassium para-aminobenzoate (Potaba) is believed to have an antifibrotic effect by decreasing the concentration of serotonin, which contributes to fibrogenesis. […] Tamoxifen inhibits the release of transforming growth factor alpha and beta from human fibroblast, which leads to reduced inflammatory response in lesions and reduced plaque size through the inhibition of angiogenesis and fibrogenesis. […] Acetyl-L-carnitine is hypothesized to prevent proliferation of fibroblast and collagenogenesis by reducing free radicals and intracellular calcium concentration. […] PDE5 inhibitors are speculated to prevent plaque development and reduce its size through maintaining a high level of cyclic guanosine monophosphate in the target tissue, which has an anti-fibrotic effect.
  • #1 Peyronie’s Disease Guideline – American Urological Association
    https://www.auanet.org/guidelines-and-quality/guidelines/peyronies-disease-guideline
    Basic scientific investigation effort should be geared toward elucidating the biologic mechanisms of PD. Current understanding of pathogenesis suggests the involvement of inflammatory factors, cytokines, growth factors and other molecular factors involved in tissue injury, fibrosis and abnormal wound healing. Ongoing scientific investigation that defines the molecular pathophysiology of this disorder can be expected to suggest molecular sites that can be targeted therapeutically. In acknowledgment of a likely genetic determinant or susceptibility for many individuals incurring PD, scientific focus should be intensified in discovering the genetic factors related to this condition. Investigative work involving gene expression profiles and describing gene mutations of cellular proteins involved in tissue fibrosis and plaque calcification is most relevant. Such work also may lead to establishing biomarkers that can be applied for disease evaluation and related diagnostic procedures (e.g., predictors of progression, spontaneous recovery, and possibly treatment response). Purpose in the basic scientific arena also may encompass the application of emerging technologies which, while grounded within advancements in the scientific basis of PD, may yield opportunities for implementing revolutionary therapeutics in the field. Besides such advances in pharmacotherapy, gene therapy, stem cell therapy and regenerative medicine may all be considered as having potential future roles in this condition.
  • #1 Treatment of Peyronie’s Disease with Stem Cell
    https://dreminozbek.com/en/treatment-of-peyronies-disease-with-stem-cell/
    Peyronies disease is a condition characterized by the development of fibrous scar tissue inside the penis, leading to curvature, pain, and sometimes erectile dysfunction. […] However, emerging research suggests that stem cell therapy could offer a promising avenue for treating Peyronies disease. […] In the context of Peyronies disease, stem cell therapy aims to harness this regenerative potential to repair the damaged tissue in the penis. […] The mechanism of action of stem cell therapy for Peyronies disease involves several key processes that contribute to tissue repair and regeneration within the penis: […] Stem cells possess anti-inflammatory properties, which help to reduce inflammation in the penile tissue affected by Peyronies disease. […] By injecting stem cells directly into the affected area of the penis, the goal is to modulate inflammation, reduce scar tissue formation, and potentially improve penile curvature, pain, and erectile function.
  • #1 Treatment of Peyronie’s Disease with Stem Cell
    https://dreminozbek.com/en/treatment-of-peyronies-disease-with-stem-cell/
    Stem cells have the unique ability to differentiate into various cell types, including smooth muscle cells, endothelial cells, and fibroblasts, which are essential for tissue repair and regeneration. […] Stem cells secrete various factors and enzymes that help to remodel the extracellular matrix, breaking down scar tissue and promoting the synthesis of new, healthy tissue. […] By enhancing blood flow to the penis, stem cells improve tissue oxygenation and nutrient delivery, facilitating healing and regeneration. […] Stem cells have immunomodulatory properties, meaning they can modulate the immune response and promote tissue tolerance.
  • #2 Peyronie’s disease: a literature review on epidemiology, genetics, pathophysiology, diagnosis and work-up – Al-Thakafi – Translational Andrology and Urology
    https://tau.amegroups.org/article/view/10408/html
    Peyronies disease (PD), a fibromatous disorder of the tunica albuginea of the penile corpus cavernosum, named after the French physician Francois de la Peyronie, is characterized by pain, plaque formation, penile curvature, and plaque calcification. […] Tunical mechanical stress and microvascular trauma are major contributory factors to the pathophysiology of PD. […] The exact etiology of PD is not clearly understood, and out of numerous theories proposed, penile trauma is postulated to be a major causative factor. […] The anatomy of the vascular network around the tunica albuginea is unique. […] The most widely accepted theory is trauma or microtrauma to the tunica albuginea during erection in genetically susceptible individuals. […] Repeated microvascular injury to the tunica albuginea causes inflammation, disruption of the elastic fibers and deposition of fibrin.
  • #2 The pathophysiology of Peyronie’s disease
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4442979/
    The initiation of the disease is accepted as the extravasation of fibrinogen, converted to fibrin with the aid of thrombin, in the intralaminar space in the TA before the inflammation and fibrosis of both the plaque and normal-looking TA. […] Devine and Horton hypothesised that PD is caused by an abnormal fibrotic reaction to minimal trauma. […] These findings support the notion that entrapment of inflammatory cells and the deposition of extracellular matrix in the multi-layered structure of the TA is the key factor in inducing PD. […] There is reportedly an increase in oxidative stress in fibrogenesis, and an increase in connective tissue disorders in chronic disease states of hepatic, pulmonary and nervous system tissue degeneration. […] Important factors in the pathogenesis of PD include the regulation of collagen synthesis by many endogenous and exogenous factors, particularly those that produce oxygen-free radicals.
  • #2 Oxidative Mechanism of Peyronie’s Disease and Effectiveness of Pentoxifylline in the Therapeutic Management: A Narrative Review
    https://www.mdpi.com/2076-3921/14/2/208
    Peyronie’s disease (PD) is a chronic disease characterized by the development of fibrous tissue in the tunica albuginea of the penile corpora cavernosa that causes penile deformity. […] The precise cause of PD is not completely understood, but it is generally believed to be initiated by a specific injury in the affected area. […] Research has consistently shown that oxidative stress (OS) is a key player in PD. […] The exact cause of PD is not fully understood, but it is commonly thought to be triggered by a specific injury in the affected area. […] Although PD can be triggered by coital sexual trauma or injury, in 70% of cases, no specific cause is found, and patients do not remember the traumatic event. […] Following an injury, fibrin is deposited, and a hematoma forms. […] However, in individuals with a genetic predisposition, the hematoma that forms triggers the activation of inflammatory cells and pro-inflammatory cytokines, leading to the subsequent formation of an area of chronic inflammatory tissue that inevitably progresses to fibrosis (plaque).
  • #2 Understanding the cellular basis and pathophysiology of Peyronie’s disease to optimize treatment for erectile dysfunction – Campbell – Translational Andrology and Urology
    https://tau.amegroups.org/article/view/12563/html
    Erectile dysfunction (ED) is often associated with Peyronies disease (PD), which is an abnormal curvature of the penis. […] The pathophysiology of PD is incompletely understood, but has been studied extensively and based on our current understanding of PD physiology, many medical treatment options have been proposed. […] The precise mechanism underlying the relationship between PD and ED is unknown and their remains controversy in the current literature. […] Penile microtrauma is thought to be the triggering event for the majority of PD. […] In the chronic phase of PD plaque formation, the fibrosis accelerates and impedes the erectile tissue, and therefore often results in ED. […] Imaging studies in men with PD and ED reveal at least one-third have arterial insufficiency and almost 60% have veno-occlusive disease.
  • #2 Can Peyronie’s Disease Be Inherited?
    https://www.healthline.com/health/mens-health/peyronies-disease-inherited
    Peyronies disease may run in families and be linked to autoimmune conditions and connective tissue disorders. […] While scientists dont know exactly what causes Peyronies disease, it often happens after an injury to the penis, sometimes during sex. Evidence suggests that genes may also be involved because the condition sometimes runs in families. […] The genes that are involved might cause thickening and scarring of connective tissue. But exactly which genes those are is still a mystery. […] Those findings suggest that gene changes called mutations may play a role in causing the disorder. […] A 2022 study showed that the risk of Peyronies was much higher in first-degree relatives (parents, siblings, children) than in non-relatives. […] Genes related to Peyronies disease may pass from father to son. If your father has this condition, youre more likely to develop it.
  • #2 Epigenetic Profiles of Men With Peyronie’s Disease – American Urological Association
    https://auanews.net/issues/articles/2024/june-extra-2024/epigenetic-profiles-of-men-with-peyronies-disease
    Peyronie’s disease (PD) is a fibrosing disorder with a prevalence of up to 11% in the United States. This evidence supports a pathophysiology centered on a genetic predisposition towards fibrosis in a subset of men, rather than a set of isolated fibrotic conditions brought about by discrete traumatic occurrences. […] Epigenetic regulation involving histone deacetylases (HDAC) has already been implicated in the pathogenesis of multiple fibrotic disorders of the kidneys, bladder, lungs, heart, and liver and has subsequently been found to play a significant role in PD, including the extent of fibrosis that may occur after disease onset. […] This suggests that variations in methylation and subsequent gene expression without overt genetic defects may predispose men to the condition and can be targets for treatment.
  • #2 The pathophysiology of Peyronie’s disease
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4442979/
    TGF- has recently received attention as a cytokine influencing the deposition of extracellular matrix, and inducing fibrosis in the TA. […] The overexpression of myostatin, a member of TGF- family, has been found in PD plaques, and it induced new plaque when induced, and condensed the plaque already formed by TGF- 1. […] The inhibition and lack of collagenases contribute to the PD process, while iNOS, matrix metalloproteinases (MMP)-2 and -9, decorin and thymosins are the active defence mechanisms against the disease. […] The persistence of myofibroblasts which are removed by apoptosis was investigated in a recent study in which the expressions of apoptotic genes were investigated. […] In relation to the therapeutic benefits of understanding the pathophysiological mechanisms of PD, Jang et al. reported that the overexpression of TGF- and activation of Smad transcriptional factors are known to be crucial in the pathogenesis of PD.
  • #2 Peyronie’s disease: a literature review on epidemiology, genetics, pathophysiology, diagnosis and work-up – Al-Thakafi – Translational Andrology and Urology
    https://tau.amegroups.org/article/view/10408/html
    The influx of leukocytes and macrophages, as an inflammatory response, continues via arterial flow, resulting in production of a large amount of cytokines. […] The above theories attempt to explain that PD is caused due to aberrant wound-healing process, in response to trauma within the layers of tunica albuginea. […] Fibrogenesis in many chronic hepatic, pulmonary, and neuronal degeneration diseases is caused due to oxidative stress. […] Increased expression of TGF-1 and higher levels of pro-and anti-fibrotic gene products could be observed in PD. […] TGF-1 is a soluble growth factor of the TGF- superfamily, and binds to specific serine/threonine kinase receptors on cell surface, triggering the activation of Smad transcription factors. […] A complicated signaling network of Smad transcription factors regulates the profibrotic effects of TGF-.
  • #2 Molecular Mechanisms and Risk Factors Related to the Pathogenesis of Peyronie’s Disease
    https://www.mdpi.com/1422-0067/24/12/10133
    TGF-β is stored in a latent form in most normal tissues, while upon tissue injury, de novo synthesis of TGF-β isoforms and latent stores of TGF-β are activated. […] Indeed, activation of TGF-β signaling through the subtunical injection of TGF-β1 in rat and rabbit models has been demonstrated to induce PD-like plaque formation in the penis. […] TGF-β signaling includes SMAD-mediated canonical and non-canonical TGF-β signaling pathways. […] The TGF-β/SMAD signaling pathway is regulated by feedback inhibition to control cellular homeostasis. […] These observations were supported by other later studies. […] The profibrotic mechanism of TGF-β1-induced PI3K/AKT signaling involves the inactivation of NR4A1, which inhibits the expression of profibrotic genes. […] Therefore, parallel non-regulated activity of several core pathways, with TGF-β signaling pathway as the main axis, that simultaneously leads to altered signaling crosstalk can conceivably result in the development of PD via aberrant tissue repair and fibrosis in TA tissues.
  • #2 Peyronie Disease | Treatment & Management | Point of Care
    https://www.statpearls.com/point-of-care/111973
    Abnormal inflammation and wound healing are believed to be responsible for the increased cellularity around the tunica, which results in a perivascular lymphocytic infiltrate around or within the tunica itself. […] These effects collectively result in an inflammatory cascade that promotes localized fibrosis and plaque formation over normal wound consolidation. […] Other theories have been suggested to explain the formation of the plaques, including microtrauma, microvasculature injury, chromosomal instability of fibroblasts involved in plaque formation, aberrations in the inducible nitric oxide pathways, and patient HLA subtype. […] There is evidence that crosstalk may be involved between TGF-, WNT/-catenin, Hedgehog, YAP/TAZ, MAPK, ROCK, and PI3K/AKT signaling pathways.
  • #2 Peyronie’s disease: a literature review on epidemiology, genetics, pathophysiology, diagnosis and work-up – Al-Thakafi – Translational Andrology and Urology
    https://tau.amegroups.org/article/view/10408/html
    Myostatin is a member of TGF- family also known as GDF-8. […] Overexpression of myostatin has been found in the majority of the PD plaques. […] This evidence suggests that PD plaques and other related symptoms are developed due to various conditions, and there is no exact and clear pathophysiology.
  • #2 Understanding the cellular basis and pathophysiology of Peyronie’s disease to optimize treatment for erectile dysfunction – Campbell – Translational Andrology and Urology
    https://tau.amegroups.org/article/view/12563/html
    Mechanical trauma and oxidative stress are the key initiators of the fibrotic pathway. […] Penile microtrauma during sexual activity is the most common trigger for fibrosis associated with PD. […] The regulation of collagen synthesis by many endogenous and exogenous peptides are key in the pathogenesis of PD. […] The overexpression of TGF- has been observed in PD plaques. […] The lack of fibrinolytic enzymes and vascular structure in the TA allow the protein itself to act as a strong chemo-attractant and therefore promote the ingrowth of cytokines, fibroblasts and inflammatory cells. […] Chronic inflammation and excessive tissue repair trigger an accumulation of ECM components, which leads to the formation of a permanent fibrotic scar. […] Fibrosis occurs when the synthesis of new collagen by myofibroblasts exceeds the rate at which it is degraded, such that the total amount of collagen increases over time.
  • #2 Oxidative Mechanism of Peyronie’s Disease and Effectiveness of Pentoxifylline in the Therapeutic Management: A Narrative Review
    https://www.mdpi.com/2076-3921/14/2/208
    Histologically, the Peyronie’s plaques are characterized by a disorganization of collagen associated with a reduction in the density of elastin. […] Numerous studies have demonstrated that oxidative stress (OS) is a crucial factor in all types of inflammatory processes, whether they are acute or chronic. […] Research has consistently shown that OS is a key player in PD, a condition characterized by chronic inflammation in the penile corpora cavernosa. […] The most important biological mediators in the pathogenesis of PD are as follows: reactive oxygen species (ROS), reactive nitrogen species (RNS), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), transforming growth factor beta-1 (TGF-β1), platelet-derived growth factor (PDGF), interleukin-1 (IL-1), basic fibroblast growth factor (bFGF), plasminogen activator inhibitor-1 (PAI-1), and tumor necrosis factor-alpha (TNF-α).
  • #2 Peyronie’s disease: an anatomically-based hypothesis and beyond | International Journal of Impotence Research
    https://www.nature.com/articles/3900876
    In my opinion, Peyronie’s disease is aberrant wound healing in response to an inflammation trapped within the layers of tunica albuginea. […] When a blunt trauma breaks the fibers of the tunica with extravasation, the resulting inflammatory response creates an area of edema and cell infiltration which compress the nearby venous channels and forming a trapped inflammatory response. […] While the secretions from leukocytes and macrophages such as elastases break the elastic fibers, the cytokines such as transforming growth factor beta (TGFb) released by the same cells stimulate production of intercellular matrix and collagen fibers. […] The unique ability of TGFb to produce more of itself forms a vicious cycle within this microenvironment and results in excessive production of intercellular matrix and collagen fibers.
  • #2 What causes Peyronies’s Disease?
    https://www.andrology.co.uk/peyronies-disease/what-causes-peyronies-disease
    At present, the actual mechanism causing Peyronies disease is still unknown. […] It is suspected that this condition occurs in the genetically predisposed patient following a trauma to the erect penis. Possibly patients with Peyronies Disease present an imbalance in the factors promoting the healing process after a trauma and this leads to excessive local tissue proliferation following a trauma. Typically Peyronies Disease presents an initial acute and a chronic phase. The acute phase is characterized by the formation of the plaque, which is tender at palpation as there is an active local inflammatory process. During this phase, stretching of the plaques, as physiologically occurs during erections, elicits vivid pain. […] The chronic phase starts when the inflammatory process eventually settles, usually around 3 to 9 months from the onset of the condition. At this stage the pain generally settles and the deformity stabilizes.
  • #2 Peyronie’s Disease | SpringerLink
    https://link.springer.com/chapter/10.1007/978-3-031-11701-5_6
    The altered repair processes of the first phase result in the formation of dense fibrotic plaques which may also progress to calcification, stabilizing, or worsening the penile curvature. […] Current knowledge on the matter of molecular pathways of inflammation and fibrosis still seems not enough clear. Indeed, penile trauma does not always result in PD, and PD patients do not always have a history of penile trauma. This fact, along with an uneven prevalence across ethnicities and the noted correlations with other fibroproliferative diseases, has prompted research in genetics, mainly in the fields of HLA group antigens, autoimmunity, single nucleotide polymorphisms and karyotype aberrations. Nevertheless, results in this field have been inconclusive.
  • #2 Peyronie’s disease: an anatomically-based hypothesis and beyond | International Journal of Impotence Research
    https://www.nature.com/articles/3900876
    The final outcome is a prolonged inflammatory response with total breakdown of the delicately arranged network of collagen and elastic fibers and excessive production of collagen fibers. […] In chronic phase, if the fibrosis has begun to encroach upon the erectile tissue, erectile dysfunction may occur. […] These phenomena may contribute to the clinical presentation of Peyronie’s disease in which the early phase triad consists of pain, plaque and penile deformity and the late triad consists of plaque, penile deformity and erectile dysfunction.
  • #2 Peyronie Disease – StatPearls – NCBI Bookshelf
    https://www.ncbi.nlm.nih.gov/books/NBK560628/
    Wound healing is delayed and becomes unregulated due to the prolonged inflammation. The enhancement of fibrous tissue production is mediated by TGF-1, PAI-1, PDGF, IL-1, and IL-6. […] These effects collectively result in an inflammatory cascade that promotes localized fibrosis and plaque formation over normal wound consolidation. […] Other theories have been suggested to explain the formation of the plaques, including microtrauma, microvasculature injury, chromosomal instability of fibroblasts involved in plaque formation, aberrations in the inducible nitric oxide pathways, and patient HLA subtype. […] There is evidence that crosstalk may be involved between TGF-, WNT/-catenin, Hedgehog, YAP/TAZ, MAPK, ROCK, and PI3K/AKT signaling pathways. […] Plaque calcification, primarily composed of calcium phosphate, occurs due to increased TGF-1 activity, which enhances osteogenesis and upregulates pleiotrophin, an osteogenic growth factor that stimulates fibroblast and osteoblast activity.
  • #2 Oxidative Mechanism of Peyronie’s Disease and Effectiveness of Pentoxifylline in the Therapeutic Management: A Narrative Review
    https://www.mdpi.com/2076-3921/14/2/208
    The production of ROS triggers the activation of NF-κB, which controls DNA transcription and specifically regulates the expression of genes such as TGF-β1, bFGF, fibrin, collagen, and inducible nitric oxide synthase (i-NOS), among others. […] TGF-β1 is a cytokine secreted by macrophages, platelets, T lymphocytes, and neutrophils. […] TGF-β1 carries out the following actions: It attracts neutrophils, monocytes, lymphocytes, and fibroblasts; promotes fibroblast growth and their transformation into myofibroblasts; induces collagen production by fibroblasts; stimulates collagen synthesis and deposition; promotes osteogenesis in the PD plaque; and enhances the production of tissue inhibitors of matrix metalloproteinases (TIMP-1). […] PTX has several mechanisms of action, including antioxidant, antifibrotic, anti-inflammatory, and vasorelaxant.
  • #2 Peyronie Disease: Practice Essentials, Problem, Epidemiology
    https://emedicine.medscape.com/article/456574-overview
    Peyronie disease (PD) is characterized by curvature in the penile shaft that is often preceded by painful erections and accompanied by an area of fibrosis. […] The etiology of PD remains enigmatic. PD has been associated with deficiency in vitamin E, ingestion of beta-blocking agents, and elevations of serotonin levels. PD is associated with Dupuytren contractures and with HLA-B7, implying a genetic link to its etiology. […] More recently, PD has been thought to result from vascular trauma or injury to the penis. The injury may be trivial or involve only microscopic vessels and tissues. This triggers the release of cytokines that activate fibroblast proliferation and produce collagen, the main matrix component of a Peyronie plaque, within the tunica albuginea. […] In PD, the initial inflammatory response is characterized by chronic lymphocytic and plasmacytic infiltration of the tunica albuginea. This may be the result of minor penile trauma, as can happen unnoticed during intercourse.
  • #2 Peyronie’s Disease | SpringerLink
    https://link.springer.com/chapter/10.1007/978-3-031-11701-5_6
    The underlying mechanisms are thought not to be exclusive to PD, given a significant overlap in pathology, occurrence, and epidemiology between PD and other localized fibrosing afflictions such as Dupuytren and Ledderhose disease. […] The acute phase is believed to be triggered by microtrauma delivered to the penile tunica albuginea, most commonly during sexual activity. The structure of the tunica albuginea is damaged through delamination of fascial layers. This results in a release of pro-inflammatory mediators (TGF-, IL-1, FGF, PDGF, PAI-1 as well as reactive oxygen species) involved in wound healing which generate platelet aggregation, clot formation, and local recruitment of inflammatory cells. […] Alterations in the levels of growth factors and cytokines released in these instances are responsible for the imbalance between extracellular matrix (ECM) deposition, myofibroblast proliferation, and myofibroblast apoptosis which is at the core of this phase.
  • #2 Molecular Mechanisms and Risk Factors Related to the Pathogenesis of Peyronie’s Disease
    https://www.mdpi.com/1422-0067/24/12/10133
    Peyronie’s disease (PD) is a benign condition caused by plaque formation on the tunica albuginea of the penis. […] In recent years, research into understanding of the detailed mechanisms and risk factors involved in the development of PD has been increasing. In this review, the pathological mechanisms and several closely related signaling pathways, including TGF-β, WNT/β-catenin, Hedgehog, YAP/TAZ, MAPK, ROCK, and PI3K/AKT, are described. […] Although the exact etiology of PD remains unknown, evidence accumulated over the past two decades shows several molecular alterations and aberrant signaling pathways involved in the pathogenesis. […] A better understanding of both related molecular mechanisms and multifactorial factors associated with PD pathogenesis will have a major influence on treatment options as well as prevention strategies.
  • #2 Peyronie’s disease | Dr. Enrique Lledó
    https://doctorlledo.com/en/peyronies-disease/
    Peyronies disease is a disorder in which scar tissue, called fibrous plaque, forms in the penis. The plaque accumulates, specifically, in a thick, elastic membrane called the tunica albuginea, which surrounds the corpora cavernosa of the penis, the structures that during erection fill with blood upon sexual arousal and make the penis rigid. […] To understand the mechanism that generates this fibrous plaque enveloping the corpus cavernosum, we can imagine what would happen if we add a strip of zeal around a sausage-shaped balloon and try to inflate it (it will deform and bend). […] Peyronies disease begins with inflammatory changes and may develop into a fully calcified lesion. […] Peyronies disease can lead to a shortening of penile length, so consistency in treatment is essential. […] Collagenase can help break up scar tissue and decrease plaque size and curvature.
  • #2 Oxidative Mechanism of Peyronie’s Disease and Effectiveness of Pentoxifylline in the Therapeutic Management: A Narrative Review
    https://www.mdpi.com/2076-3921/14/2/208
    The studies have shown us that PTX is able to reduce the symptoms of the disease, including curvature, pain, and erectile dysfunction. […] In our studies, we have shown multiple times that it is not only possible to treat this disease but to regress it with the administration of oral antioxidants, combining them with the penile injection of pentoxifylline.
  • #2 Treatment of Peyronie’s Disease with Stem Cell
    https://dreminozbek.com/en/treatment-of-peyronies-disease-with-stem-cell/
    Peyronies disease is a condition characterized by the development of fibrous scar tissue inside the penis, leading to curvature, pain, and sometimes erectile dysfunction. […] However, emerging research suggests that stem cell therapy could offer a promising avenue for treating Peyronies disease. […] In the context of Peyronies disease, stem cell therapy aims to harness this regenerative potential to repair the damaged tissue in the penis. […] The mechanism of action of stem cell therapy for Peyronies disease involves several key processes that contribute to tissue repair and regeneration within the penis: […] Stem cells possess anti-inflammatory properties, which help to reduce inflammation in the penile tissue affected by Peyronies disease. […] By injecting stem cells directly into the affected area of the penis, the goal is to modulate inflammation, reduce scar tissue formation, and potentially improve penile curvature, pain, and erectile function.
  • #3 The pathophysiology of Peyronie’s disease
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4442979/
    To review the contemporary knowledge of the pathophysiology of Peyronies disease (PD). […] Many theories have been proposed to explain the cause of PD, but the true pathogenesis of PD remains an enigma. Identifying particular growth factors and the specific genes responsible for the induction of PD have been the ultimate goal of research over the past several decades. […] The pathogenesis of PD has been explored in animal models, cell cultures and clinical trials, but the results have led to further questions. New research on the aetiology and pathogenesis of PD is needed, and which will hopefully improve the understanding and management for patients with this frustrating disease. […] The pathogenesis remains uncertain and there is still controversy about the best management. […] PD can thus be considered as an aberrant wound-healing process in response to an inflammation constrained within the many layers of the TA.
  • #3 Molecular Mechanisms and Risk Factors Related to the Pathogenesis of Peyronie’s Disease
    https://www.mdpi.com/1422-0067/24/12/10133
    The hypothesis posed by Devine et al. that PD is initiated by repetitive micro-trauma to the penis during intercourse has become widely accepted. […] For affected patients, the primary site of injury is thought to be the TA, with disruption of the inner and outer layers creating a milieu for inflammation, elastic fiber disruption, and extravascular blood accumulation. […] Transforming growth factor-β1 (TGF-β1) is a key factor for myofibroblast activation and a major player in fibrosis in all organs. […] An imbalance between matrix metalloproteinase (MMP), which removes collagen fibers, and its tissue inhibitor of metalloproteinase (TIMP) in myofibroblasts, along with the evasion of apoptosis, are thought to be key factors in the development of fibrotic diseases. […] Based on the latest reported findings, details regarding the mechanisms of fibrotic tissue remodeling and putative functions of each cell type during different stages of PD are presented below.
  • #3 Understanding the cellular basis and pathophysiology of Peyronie’s disease to optimize treatment for erectile dysfunction – Campbell – Translational Andrology and Urology
    https://tau.amegroups.org/article/view/12563/html
    The devastating sexual and psychological impact PD has on patients necessitates improved treatment and prevention strategies. […] Our current therapies frequently do not meet expectations and therefore to further develop new strategies, we need a complete understanding of the precise cellular and pathophysiologic processes of PD and gather knowledge of how we can intervene at a molecular level. […] PD is a wound-healing disorder, similar to keloids, hypertrophic scars, or Dupuytrens contractures, all of which may be coinciding findings. […] The dense plaques identified in PD are a result of an imbalance of fibrosis and fibrinolysis. […] Fibrosis is the result of chronic inflammation which can be induced by persistent infections, autoimmune reactions, allergic responses, chemical insults, radiation, and tissue injuries.
  • #3 Epigenetic Profiles of Men With Peyronie’s Disease – American Urological Association
    https://auanews.net/issues/articles/2024/june-extra-2024/epigenetic-profiles-of-men-with-peyronies-disease
    Peyronie’s disease (PD) is a fibrosing disorder with a prevalence of up to 11% in the United States. This evidence supports a pathophysiology centered on a genetic predisposition towards fibrosis in a subset of men, rather than a set of isolated fibrotic conditions brought about by discrete traumatic occurrences. […] Epigenetic regulation involving histone deacetylases (HDAC) has already been implicated in the pathogenesis of multiple fibrotic disorders of the kidneys, bladder, lungs, heart, and liver and has subsequently been found to play a significant role in PD, including the extent of fibrosis that may occur after disease onset. […] This suggests that variations in methylation and subsequent gene expression without overt genetic defects may predispose men to the condition and can be targets for treatment.
  • #3 Oxidative Mechanism of Peyronie’s Disease and Effectiveness of Pentoxifylline in the Therapeutic Management: A Narrative Review
    https://www.mdpi.com/2076-3921/14/2/208
    The production of ROS triggers the activation of NF-κB, which controls DNA transcription and specifically regulates the expression of genes such as TGF-β1, bFGF, fibrin, collagen, and inducible nitric oxide synthase (i-NOS), among others. […] TGF-β1 is a cytokine secreted by macrophages, platelets, T lymphocytes, and neutrophils. […] TGF-β1 carries out the following actions: It attracts neutrophils, monocytes, lymphocytes, and fibroblasts; promotes fibroblast growth and their transformation into myofibroblasts; induces collagen production by fibroblasts; stimulates collagen synthesis and deposition; promotes osteogenesis in the PD plaque; and enhances the production of tissue inhibitors of matrix metalloproteinases (TIMP-1). […] PTX has several mechanisms of action, including antioxidant, antifibrotic, anti-inflammatory, and vasorelaxant.
  • #3 Molecular Mechanisms and Risk Factors Related to the Pathogenesis of Peyronie’s Disease
    https://www.mdpi.com/1422-0067/24/12/10133
    Peyronie’s disease (PD) is a benign condition caused by plaque formation on the tunica albuginea of the penis. […] In recent years, research into understanding of the detailed mechanisms and risk factors involved in the development of PD has been increasing. In this review, the pathological mechanisms and several closely related signaling pathways, including TGF-β, WNT/β-catenin, Hedgehog, YAP/TAZ, MAPK, ROCK, and PI3K/AKT, are described. […] Although the exact etiology of PD remains unknown, evidence accumulated over the past two decades shows several molecular alterations and aberrant signaling pathways involved in the pathogenesis. […] A better understanding of both related molecular mechanisms and multifactorial factors associated with PD pathogenesis will have a major influence on treatment options as well as prevention strategies.
  • #3 Peyronie’s disease – Wikipedia
    https://en.wikipedia.org/wiki/Peyronie%27s_disease
    Peyronie’s disease develops in two phases: the acute (inflammatory) and chronic (fibrotic) phase. During the acute phase, microtrauma induces damage to the endothelium, fibrin deposition, and immigration of immune cells into the tunica albuginea. Fibroblast proliferation and myofibroblast differentiation are promoted by cytokines like TGF-1, PDGF (platelet-derived growth factor), and ROS (reactive oxygen species). Myofibroblasts overexpress type I collagen and extracellular matrix proteins, leading to plaque formation. In the chronic presentation, inflammation is reduced, but the fibrotic plaque is preserved, and partial calcification occurs in most cases. This causes structural deformity of the penile tissue and inelasticity that impedes normal growth during an erection. Intense calcification and fibrosis impair normal hemodynamics and penile elasticity of the penis, which usually causes venous leakage and erectile failure.
  • #3 Peyronie’s disease: Review of the pathology and current events in treatment
    http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S2524-177X2019000400208
    Peyronie’s disease is a medical condition characterized by an abnormal curvature of the penis, which presents a poorly understood pathophysiology, featuring abnormal fibroblasts of the tunica albuginea secondary to trauma or stemming from congenital causes. […] The development mechanism of PD is unknown. However, one of its causes can be due to a prolonged and sustained inflammatory response, triggered by trauma, which allows extravascular protein deposition, inflammatory cell recruitment, fibrin deposition on the expression of inflammatory cytosines, and release of elastase, which leads to a change of type I collagen into type III collagen. Overexpression of transforming growth factor (TGF)-B and interleukin (IL)-6 has been reported together with a lower number of blood vessels and reduced apoptosis in the histopathological samples of patients with PD.
  • #3 Peyronie’s disease: Review of the pathology and current events in treatment
    http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S2524-177X2019000400208
    Currently, the active role of free radicals is recognized as inducing an important inflammatory response, favoring the first stage of this disease. There is an important expression of pro-inflammatory and pro-fibrotic cytosines, with subsequent activation of the NF-kB factor. […] Another hypothesis states that it is a scar tissue disorder developed by genetic susceptibility, based on documentary evidence of variations in the TGF-beta 1 gene and expression of SMAD transcription factors, which regulate the mechanisms of fibrosis. The histological features of PD show lymphocytic and plasmacytic infiltrate of the tunica albuginea, as well as of the erectile tissues.
  • #3 Azthena logo with the word Azthena
    https://www.news-medical.net/health/Penile-Curvature-Peyronies-Disease-Dupuytrens-Contracture.aspx
    Peyronie’s disease is due to the formation of a fibrous band inside the penis which restricts the normal enlargement that accompanies erection. […] The injury may possibly not be acute, but rather a series of repeated injuries due to vascular blockages, minor trauma during athletic movement or even intercourse. […] Colchicine inhibits actively growing cells and is supposed to prevent fibroblast proliferation and fibrous tissue deposition. Verapamil is usually used to treat hypertension, but is helpful in Peyronie’s disease by breaking down a protein involved in scarring. […] Recently an injectable form of the collagenase enzyme from the bacterium Clostridium histolyticum has been used successfully to treat this condition. This enzyme breaks up the fibrous collagen tissue of the scar.

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