Statins and myocardial hypertrophy.
Cardiac hypertrophy is a physiological adaptive response by the heart to pressure overload. However, after prolonged periods, this initial adaptive response becomes maladaptive, leading to increased mortality and morbidity from heart failure. Recently, 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, have been shown to inhibit cardiac hypertrophy by cholesterol-independent mechanisms. Statins block the isoprenylation and activation of members of the Rho guanosine triphosphatase (GTPase) family, such as RhoA and Rac1. Since Rac1 is a requisite component of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which is a major source of reactive oxygen species (ROS) in cardiovascular cells, the ability of statins to inhibit Rac1-mediated oxidative stress makes an important contribution to their inhibitory effects on cardiac hypertrophy.
Nakagami
Hironori
H
Vascular Medicine Research, Brigham and Women's Hospital and Harvard Medical School, Cambridge, Massachusetts 02139, USA.
Liao
James K
JK
D000818:Animals; D006332:Cardiomegaly / Q000517:prevention & control*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D020559:Monomeric GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D019255:NADPH Oxidases / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019255:NADPH Oxidases; D020559:Monomeric GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein