{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:19:11Z","timestamp":1791227951712,"version":"4.1.0"},"reference-count":40,"publisher":"American Veterinary Medical Association (AVMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2011,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Objective<\/jats:bold>\u2014To investigate the roles of transforming growth factor-\u03b2 (TGF-\u03b2) isoforms and matrix metalloproteinases (MMPs) in development of chronic mitral valvular disease (CMVD) in dogs.<\/jats:p>\n<jats:p><jats:bold>Sample Population<\/jats:bold>\u201412 mitral valve leaflets collected from cadavers of 5 clinically normal dogs and from 7 dogs with CMVD.<\/jats:p>\n<jats:p><jats:bold>Procedures<\/jats:bold>\u2014Expression of TGF-\u03b2 isoforms 1, 2, and 3; MMPs 1, 2, 3, and 9; TGF-\u03b2 receptor II (T\u03b2R-II); and \u03b1 smooth muscle actin (\u03b1SMA) in mitral valves of dogs with CMVD was compared with that in mitral valves from clinically normal dogs. Additionally, responses of valvular interstitial cells (VICs) to TGF-\u03b23, MMP-3, and angiotensin-converting enzyme inhibitor (ACEI) as a suppressor of TGF-\u03b23 were examined in vitro.<\/jats:p>\n<jats:p><jats:bold>Results<\/jats:bold>\u2014Expression of TGF-\u03b23, T\u03b2R-II, \u03b1SMA, and MMP-3 was only detected in mitral valves of dogs with CMVD. Concentrations of \u03b1SMA and proteoglycans in cultured VICs were significantly increased following incubation with TGF-\u03b23; treatment with MMP-3 resulted in increased amounts of active and total TGF-\u03b23, and total TGF-\u03b23 in VICs was significantly decreased by incubation with ACEI.<\/jats:p>\n<jats:p><jats:bold>Conclusions and Clinical Relevance<\/jats:bold>\u2014Findings suggested that increased TGF-\u03b23 and MMP-3 contribute to the pathogenesis of valvular degeneration associated with CMVD. In addition, it is possible that the use of ACEI could effectively block pathological alterations in VICs associated with CMVD in vitro.<\/jats:p>\n<jats:p><jats:bold>Impact on Human Medicine<\/jats:bold>\u2014CMVD is associated with primary mitral valve prolapse and Marfan syndrome in humans. Results of the study reported here will help to elucidate the molecular mechanisms of CMVD in dogs and humans.<\/jats:p>","DOI":"10.2460\/ajvr.72.2.194","type":"journal-article","created":{"date-parts":[[2011,2,1]],"date-time":"2011-02-01T08:03:28Z","timestamp":1296547408000},"page":"194-202","source":"Crossref","is-referenced-by-count":32,"title":["Effects of transforming growth factor-\u03b23 and matrix metalloproteinase-3 on the pathogenesis of chronic mitral valvular disease in 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