Article Text

PDF
Statin Therapy for Cardiac Hypertrophy and Heart Failure
  1. James K. Liao
  1. From Vascular Medicine Research, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA.
  2. Supported in part by grants from the National Institutes of Health (HL52233) and the American Heart Association Bugher Foundation Award. Dr. Liao is an established investigator of the American Heart Association.
  3. Presented at the Joint American Federation for Medical Research/American Society for Clinical Investigation Meeting on April 17, 2004, Chicago, IL. Dr. Liao is a recipient of the 2005 AFMR Outstanding Investigator Award.
  4. Address correspondence to: Dr. James K. Liao, Vascular Medicine Research, Brigham & Women's Hospital, 65 Lands-downe Street, Room 275, Cambridge, MA 02139; e-mail: jliao{at}rics.bwh.harvard.edu.

Abstract

Cardiac hypertrophy leading to heart failure is a major cause 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 guanosine triphosphatase family, such as Rac1 and RhoA. Because Rac1 is a requisite component of reduced nicotinamide adenine dinucleotide phosphate 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 up-regulation of endothelial nitric oxide synthase in the endothelium and the heart. This results in increased angiogenesis and myocardial perfusion, decreased myocardial apoptosis, and improvement in endothelial and cardiac function. Because these effects of statins occur independently of cholesterol lowering, statins may have therapeutic benefits in nonhyperlipidemic patients with cardiac hypertrophy and heart failure.

Key Words
  • cardiac hypertrophy
  • heart failure
  • G proteins
  • protein kinase Akt
  • nitric oxide

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.