{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:21:37Z","timestamp":1790032897197,"version":"4.0.1"},"reference-count":221,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>\n                    The mitral valve apparatus comprises the annulus, valve leaflets, chordae tendineae, and papillary muscles, forming an integrated biomechanical unit essential for unidirectional blood flow. The leaflets and chordae are primarily derived from endocardial cells, and damage to these structures results in either mitral stenosis or mitral regurgitation, depending on the underlying pathology. This review compares three major mitral valve diseases, rheumatic mitral stenosis, congenital mitral stenosis, and myxomatous mitral valve prolapse, to highlight their distinct etiologies, molecular mechanisms, and structural endpoints. Rheumatic mitral stenosis is an acquired immune-mediated disease triggered by Group A streptococcal infection, in which molecular mimicry leads to autoantibody formation and chronic inflammation. Immune-cell infiltration and cytokine release drive the progression of leaflet fibrosis, commissural fusion, calcification, and pronounced chordal shortening, ultimately culminating in fixed obstruction. Large-scale genetic studies have not identified strong causal genes, instead revealing associations with immune-related risk loci, while valve-specific epigenetic mechanisms are poorly explored. Congenital mitral stenosis arises from developmental abnormalities of the mitral valve complex during embryogenesis and is classified into four anatomical subtypes. Due to its low incidence, the condition remains the least studied at the molecular and genetic levels. In contrast, myxomatous mitral valve prolapse is a degenerative, polygenic disorder driven by aberrant TGF\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -dependent endothelial-to-mesenchymal transformation, valve interstitial cell activation, and extracellular matrix remodeling. Genetic studies have identified multiple causal genes, including\n                    <jats:italic>FLNA<\/jats:italic>\n                    ,\n                    <jats:italic>DCHS1<\/jats:italic>\n                    ,\n                    <jats:italic>DZIP1<\/jats:italic>\n                    , and\n                    <jats:italic>TNS1<\/jats:italic>\n                    , underscoring its mechano-genetic origin. Despite their distinct causes, immune-mediated, developmental, and degenerative\/genetic, all three diseases converge on progressive structural failure of the MV apparatus. Notably, pathological remodeling of the chordae plays a decisive role in disease progression and the need for surgical intervention. A deeper understanding of both shared and disease-specific mechanisms, particularly valve- and chordae-specific molecular regulation, is essential to advance translational research in mitral valve disease.\n                  <\/jats:p>","DOI":"10.3389\/fcvm.2026.1773671","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T06:41:28Z","timestamp":1770187288000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Mechanisms of mitral valve development and disease"],"prefix":"10.3389","volume":"13","author":[{"given":"Enshi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, The University of Chicago","place":["Chicago, IL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of Chicago","place":["Chicago, IL, United States"]},{"name":"Departmens of Genetics, Pediatrics, and Medicine, Albert Einstein College of Medicine","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1038\/s41569-021-00570-z","article-title":"Global epidemiology of valvular heart disease","volume":"18","author":"Coffey","year":"2021","journal-title":"Nat Rev Cardiol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1016\/j.jacc.2010.04.030","article-title":"Anatomy of the mitral valvular complex and its implications for transcatheter interventions for mitral regurgitation","volume":"56","author":"Van Mieghem","year":"2010","journal-title":"J Am Coll Cardiol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1002\/ca.20692","article-title":"The clinical anatomy of the mitral valve","volume":"22","author":"Muresian","year":"2009","journal-title":"Clin Anat"},{"key":"B4","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1161\/01.CIR.46.2.227","article-title":"The mitral apparatus. 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