Modulation of transforming growth factor-β signaling and extracellular matrix productio.docVIP

surgery for Valvular Heart Disease Modulation of Transforming Growth Factor-β Signaling and Extracellular Matrix Production in Myxomatous Mitral Valves by Angiotensin II Receptor Blockers Arnar Geirsson, MD;? Mansher Singh, MD;? Rahmat Ali, MD; Hussain Abbas, MD;? Wei Li, MD;? Juan A. Sanchez, MD;? Sabet Hashim, MD;? George Tellides, MD, DPhil +Author Affiliations From the Department of Surgery (A.G., M.S., R.A., W.L., S.H., G.T.) and the Interdepartmental Program in Vascular Biology and Therapeutics (A.G., M.S., R.A., W.L., G.T.), Yale University School of Medicine, New Haven, CT; the Veterans Affairs Connecticut Healthcare System, West Haven, CT (A.G., G.T.); and the Department of Surgery, St Marys Hospital, Waterbury, CT (H.A., J.A.S.). Correspondence to Arnar Geirsson, MD,?Section of Cardiac Surgery, Yale University School of Medicine, 330 Cedar Street, BB204, PO Box 208039, New Haven, CT 06520-8039. E-mail?arnar.geirsson@yale.edu Presented at the 2011 American Heart Association meeting in Orlando, FL, November 13–17, 2011. ? Next Section Abstract Background—Little is known about the pathophysiology of myxomatous degeneration of the mitral valve, the pathological hallmark of mitral valve prolapse, associated with symptomatic mitral regurgitation, heart failure, and death. Excess transforming growth factor (TGF)-β signaling is known to cause mitral valve degeneration and regurgitation in a mouse model of Marfan syndrome. We examined if TGF-β signaling is dysregulated in clinical specimens of sporadic mitral valve prolapse compared with explanted nondiseased mitral valves and we tested the effects of angiotensin II receptor blockers on TGF-β signaling in cultured human mitral valve cells. Methods and Results—Operative specimens, cultured valve tissues, and cultured valvular interstitial cells were obtained from patients with mitral valve prolapse undergoing mitral valve repair or from organ donors without mitral valve disease. Increased extracellular matrix in dis