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(Circulation. 2004;109:97-102.)
© 2004 American Heart Association, Inc.

Basic Science Reports

Cardiac Systolic and Diastolic Dysfunction After a Cholesterol-Rich Diet

Y. Huang, MD; K.E. Walker, PhD; F. Hanley, BS; J. Narula, MD; S.R. Houser, PhD; T.N. Tulenko, PhD

From the Departments of Surgery, Biochemistry, and Molecular Pharmacology, Thomas Jefferson University College of Medicine (Y.H., T.N.T.); the Department of Physiology, Temple University School of Medicine (S.R.H.) and College of Allied Health Professions (K.E.W.); and the Department of Medicine, Division of Cardiology, MCP-Hahnemann University School of Medicine (J.N.), Philadelphia, Pa.

Correspondence to Thomas N. Tulenko, PhD, Professor, Department of Surgery, Thomas Jefferson University School of Medicine, 1205 Walnut St, Suite 605, Philadelphia, PA 19107. E-mail thomas.tulenko{at}jefferson.edu

Received May 27, 2003; revision received August 25, 2003; accepted September 2, 2003.

Background— Although hypercholesterolemia is a well-established risk factor for coronary artery disease, little is known regarding its direct effects on cardiac function.

Methods and Results— We examined the effects of cholesterol feeding (0.5%) on cardiac function in rabbits. After 10 weeks, both systolic shortening and diastolic relaxation rates were impaired without any change in aortic pressure or ventricular hypertrophy. However, sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA)-2 mRNA levels were reduced within 4 days after initiation of cholesterol feeding. After this effect, SERCA-2 protein and SERCA-mediated Ca uptake into sarcoplasmic reticulum vesicles were impaired, and the ratio of MHC-ß to MHC- mRNA increased 5-fold. Suppression of the SERCA-2 message correlated temporally with enrichment of the cardiac sarcolemma with cholesterol.

Conclusions— These data demonstrate that dietary hypercholesterolemia induces a "cholesterol cardiomyopathy" characterized by systolic and diastolic dysfunction. These alterations were independent of vascular disease and demonstrate a dietary link to cardiac dysfunction.

Key Words: heart failure • cardiomyopathy • myosin • sarcoplasmic reticulum • hypercholesterolemia

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