Dr. LeWinter has a longstanding interest in myocardial and ventricular function and remodeling in cardiomyopathy and heart failure. Current areas of interest include mechanoenergetics of the myocardium in acquired heart failure and genetic models of cardiomyopathy. A second area of interest is diastolic left ventricular function and in particular the role of the giant cytoskeleton protein titin as a determinant of left ventricular stiffness and restoring forces. A third area of interest is the effect of diabetes and hypertension on myocardial function, calcium handling, and myofilament function. The latter studies utilize samples of human myocardium obtained in the operating room. Dr. LeWinter is also the Principal Investigator of a grant designating the University of Vermont as one of nine NIH funded Regional Clinical Centers for heart failure research. As such, he is extensively involved in clinical trials in heart failure.

Separate NIH grants support each of the above areas.

Palmer BM, Noguchi T, Wang Y, Heim JR, Alpert NR, Burgon PG, Seidman CE, Seidman JG, Maughan DW, LeWinter MM: The effect of cardiac myosin binding protein C on mechanoenergetics in mouse myocardium. Circ Res 94:1615-1622, 2004

Noguchi T, Hunlich M, Begin K, LeWinter MM, VanBuren P: Altered thin filament activation of in vitro motility and force in failing human myocardium. Circulation 110: 982-987, 2004.

Mulieri L, Tischler M, Leavitt B, Ittleman F, Alpert NR, LeWinter MM: Differences in freewall and papillary muscle contractile reserve in patients with chronic mitral regurgitation and their relationship to ventricular geometry. Am J Physiol 288:H2185-91, 2005.

Toth M, Mathews DE, Ades PA, Tischler MD, VanBuren P, Previs M, LeWinter M: Skeletal muscle myofibrillar protein metabolism in heart failure: Relationship to immune activation and functional capacity. Am J Physiol 288:E685-92, 2005.

Fukagawa NK, Palmer BM, Barnes WD, Leavitt BJ, Ittleman FY, LeWinter MM, Mulieri LA, Maughan DW: Actomyosin crossbridge kinetics in humans with coronary artery disease: Influence of sex and diabetes mellitus. J Mol Cell Cardiol 39:743-53, 2005.

Palmer BM, Maughan DW, Hendley E, LeWinter MM: Influence of hyperactivity and/or hypertension on cardiomyocyte function in genetic models of LV hypertrophy. Am J Physiol Heart Circ Physiol 290:H463-73, 2006.

LeWinter MM, Wu Y, Labeit S, Granzier H:  Cardiac titin:  Structure, functions and role in disease.  Clin Chim Acta 375:1-9, 2007.

Suzuki T, Palmer BM, James J, Wang Y, Chen Z, VanBuren P, Maughan DW, Robbins J, LeWinter MM: Effects of cardiac myosin isoform variation on myofilament function and cross-bridge kinetics in transgenic rabbits. Circ Heart Fail 2:334-41, 2009.  

LeWinter MM,  Popper J, McNabb M, Nyland L, Stephen SB, Granzier H: Extensible behavior of titin in the miniswine left ventricle. Circulation 121:768-774, 2010.

LeWinter MM, Granzier H: Titin – A Multifunctional Giant. Circulation 121: 2137-45, 2010.

Donaldson C, Taatjes D, Palmer B, Bishop N, Von Turkovich M, Spinale F, Zile M, Maughan D, LeWinter MM: Immunoelectron microscopic detection of the advanced glycation end-product carboxymethyl lysine in human myocardium. Histochem Cell Biol 2010 May 19. [Eput ahead of print]

Savage P, Ades P, LeWinter M, Miller D, Toth M. Muscle strength and physical disability in chronic heart failure: Favorable effects of high intensity resistance training. Circ Heart Fail (in press)