doi: 10.1161/hc3001.092039
(Circulation. 2001;104:576.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Amelioration of Angiotensin II–Induced Cardiac Injury by a 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor
From the Franz Volhard Clinic and Max Delbrück Center for Molecular Medicine, Medical Faculty of the Charité, Humboldt University of Berlin (R.D., D.N.M., J.T., E.M., M.B., D.G., R.D., F.C.L.), Berlin, Germany, and Nephrology Division, Department of Medicine, Hannover Medical School (A.F., J.-K.P., H.H.), Hannover, Germany.
Correspondence to Friedrich C. Luft, MD, Charité Campus-Buch, Franz Volhard Clinic, Wiltberg Str 50, 13125 Berlin, Germany. E-mail luft{at}fvk-berlin.de
Background— 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have effects that extend beyond cholesterol reduction. We used an angiotensin (Ang) II–dependent model to test the hypothesis that cerivastatin ameliorates cardiac injury.
Methods and Results— We treated rats transgenic for human renin and angiotensinogen (dTGR) chronically from weeks 4 to 7 with cerivastatin (0.5 mg/kg by gavage). We used immunohistochemistry, electrophoretic mobility shift assays, and reverse transcription–polymerase chain reaction techniques. Compared with control dTGR, dTGR treated with cerivastatin had reduced mortality, blood pressure, cardiac hypertrophy, macrophage infiltration, and collagen I, laminin, and fibronectin deposition. Basic fibroblast growth factor mRNA and protein expression were markedly reduced, as was interleukin-6 expression. The transcription factors NF-
B and AP-1 were substantially less activated, although plasma cholesterol was not decreased.
Conclusions— These results suggest that statins ameliorate Ang II–induced hypertension, cardiac hypertrophy, fibrosis, and remodeling independently of cholesterol reduction. Although the clinical significance remains uncertain, the results suggest that statins interfere with Ang II–induced signaling and transcription factor activation, thereby ameliorating end-organ damage.
Key Words: statins • angiotensin • remodeling • cholesterol
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