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Semin Vasc Med 2004; 4(4): 377-384
DOI: 10.1055/s-2004-869594
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Statins and the Myocardium

Seema Mital1 , James K. Liao2
  • 1Division of Pediatric Cardiology, Columbia University, College of Physicians and Surgeons, New York, New York
  • 2Vascular Medicine Research, Brigham & Women’s Hospital, Harvard Medical School, Cambridge, Massachusetts
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Publikationsverlauf

Publikationsdatum:
29. April 2005 (online)

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ABSTRACT

Cardiac hypertrophy and heart failure are leading causes of morbidity and mortality worldwide. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, have been shown to inhibit cardiac hypertrophy and improve symptoms of heart failure by cholesterol-independent mechanisms. Statins block the isoprenylation and function of members of the Rho GTPase family, such as Rac1 and RhoA. Because Rac1 is a requisite component of NADPH oxidase, which is a major source of reactive oxygen species in cardiovascular cells, the ability of statins to inhibit Rac1-mediated oxidative stress contributes importantly to their inhibitory effects on cardiac hypertrophy. Furthermore, inhibition of RhoA by statins leads to the activation of protein kinase B/Akt and upregulation of Type 3 nitric oxide synthase in the endothelium and the heart. This activation and upregulation results in increased angiogenesis and myocardial perfusion, decreased myocardial apoptosis, and improvement in endothelial and cardiac function. Because these effects of statins occur independent of cholesterol lowering, statins may have therapeutic benefits in nonhyperlipidemic patients with cardiac hypertrophy and heart failure.

KEYWORDS

Cardiac hypertrophy - heart failure - G-proteins - protein kinase Akt - nitric oxide

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James K LiaoM.D. 

Director, Vascular Medicine Research, Brigham & Women's Hospital, Associate Professor of Medicine, Harvard Medical School

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