Published Online
on December 15, 2003

A more recent version of this article appeared on January 6, 2004

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Submitted on May 27, 2003
Revised on August 25, 2003
Accepted on September 2, 2003

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, and 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.

^* To whom correspondence should be addressed. E-mail: thomas.tulenko{at}jefferson.edu.

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- 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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