{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T04:08:49Z","timestamp":1790482129837,"version":"4.1.0"},"reference-count":138,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T00:00:00Z","timestamp":1652745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009147","name":"College of Medicine and Veterinary Medicine, University of Edinburgh","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009147","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>Mitral valve prolapse (MVP) due to myxomatous degeneration is one of the most important chronic degenerative cardiovascular diseases in people and dogs. It is a common cause of heart failure leading to significant morbidity and mortality in both species. Human MVP is usually classified into primary or non-syndromic, including Barlow\u2019s Disease (BD), fibro-elastic deficiency (FED) and Filamin-A mutation, and secondary or syndromic forms (typically familial), such as Marfan syndrome (MFS), Ehlers-Danlos syndrome, and Loeys\u2013Dietz syndrome. Despite different etiologies the diseased valves share pathological features consistent with myxomatous degeneration. To reflect this common pathology the condition is often called myxomatous mitral valve degeneration (disease) (MMVD) and this term is universally used to describe the analogous condition in the dog. MMVD in both species is characterized by leaflet thickening and deformity, disorganized extracellular matrix, increased transformation of the quiescent valve interstitial cell (qVICs) to an activated state (aVICs), also known as activated myofibroblasts. Significant alterations in these cellular activities contribute to the initiation and progression of MMVD due to the increased expression of transforming growth factor-\u03b2 (TGF-\u03b2) superfamily cytokines and the dysregulation of the TGF-\u03b2 signaling pathways. Further understanding the molecular mechanisms of MMVD is needed to identify pharmacological manipulation strategies of the signaling pathway that might regulate VIC differentiation and so control the disease onset and development. This review briefly summarizes current understanding of the histopathology, cellular activities, molecular mechanisms and pathogenesis of MMVD in dogs and humans, and in more detail reviews the evidence for the role of TGF-\u03b2.<\/jats:p>","DOI":"10.3389\/fcvm.2022.872288","type":"journal-article","created":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T04:39:07Z","timestamp":1652762347000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["The Role of Transforming Growth Factor-\u03b2 Signaling in Myxomatous Mitral Valve Degeneration"],"prefix":"10.3389","volume":"9","author":[{"given":"Qiyu","family":"Tang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"McNair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanchan","family":"Phadwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicky E.","family":"Macrae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan M.","family":"Corcoran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,17]]},"reference":[{"key":"B1","first-page":"76","article-title":"The significance of late systolic murmurs and mid-late systolic clicks.","volume":"12","author":"Barlow","year":"1963","journal-title":"Md State Med J."},{"key":"B2","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1111\/j.1749-6632.1965.tb33974.x","article-title":"Comparative aspects of mitral valve disease in dogs.","volume":"118","author":"Pensinger","year":"1965","journal-title":"Ann N Y Acad Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2158","DOI":"10.1161\/CIRCULATIONAHA.113.006702","article-title":"Epidemiology and pathophysiology of mitral valve prolapse new insights into disease progression, genetics, and molecular basis.","volume":"129","author":"Delling","year":"2014","journal-title":"Circulation."},{"key":"B4","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1038\/nrcardio.2015.161","article-title":"Mitral valve disease\u2013morphology and mechanisms.","volume":"12","author":"Levine","year":"2015","journal-title":"Nat Rev Cardiol."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/vetsci4030034","article-title":"Comparative transcriptomic profiling and gene expression for myxomatous mitral valve disease in the dog and human.","volume":"4","author":"Markby","year":"2017","journal-title":"Vet Sci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1093\/cvr\/cvaa062","article-title":"Macrophage lineages in heart valve development and disease.","volume":"117","author":"Kim","year":"2021","journal-title":"Cardiovasc Res."},{"key":"B7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1056\/NEJM199907013410101","article-title":"Prevalence and clinical outcome of mitral-valve prolapse.","volume":"341","author":"Freed","year":"1999","journal-title":"N Engl J Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/s0002-9343(01)00981-0","article-title":"Prevalence and correlates of mitral valve prolapse in a population-based sample of American Indians: the strong heart study.","volume":"111","author":"Devereux","year":"2001","journal-title":"Am J Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1111\/j.1749-6632.1965.tb49421.x","article-title":"The prevalence and types of cardiovascular disease in dogs.","volume":"127","author":"Detweiler","year":"1965","journal-title":"Ann N Y Acad Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1136\/vr.141.2.40","article-title":"Mortality in insured Swedish dogs: rates and causes of death in various breeds.","volume":"141","author":"Bonnett","year":"1997","journal-title":"Vet Rec."},{"key":"B11","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.jvc.2012.01.006","article-title":"Myxomatous mitral valve disease in dogs: does size matter?","volume":"14","author":"Parker","year":"2012","journal-title":"J Vet Cardiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/0002-9149(80)90232-5","article-title":"Hypertrophic cardiomyopathy. 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