TY - JOUR
T1 - Hydroxymethylglutaryl coenzyme a reductase inhibitor simvastatin prevents cardiac hypertrophy induced by pressure overload and inhibits p21ras activation
AU - Indolfi, Ciro
AU - Di Lorenzo, Emilio
AU - Perrino, Cinzia
AU - Stingone, Angela Maria
AU - Curcio, Antonio
AU - Torella, Daniele
AU - Cittadini, Antonello
AU - Cardone, Luca
AU - Coppola, Carmela
AU - Cavuto, Luigi
AU - Arcucci, Oreste
AU - Sacca, Luigi
AU - Avvedimento, Enrico Vittorio
AU - Chiariello, Massimo
PY - 2002/10/15
Y1 - 2002/10/15
N2 - Background - Patients with cardiac hypertrophy are at increased cardiovascular risk. It has been hypothesized that hydroxymethylglutaryl coenzyme A reductase inhibitors may exert beneficial effects other than their cholesterol-lowering actions. The aims of the study were to assess the in vivo effects of simvastatin (SIM) on cardiac hypertrophy and on Ras signaling in rats with ascending aorta banding. Methods and Results - Wistar rats were randomized to receive either treatment with SIM or placebo, and then short-term (group I) and long-term (group II) left ventricular pressure overload was performed by placing a tantalum clip on ascending aorta. At the end of treatment period, left and right ventricular weight, body weight, and tibial length were measured and echocardiographic evaluations were performed. Ras signaling was investigated by analyzing Ras membrane localization and activation, ERK2 phosphorylation, and p27kip1 and cdk4 levels. In SIM-treated rats, a significant reduction of left ventricular weight/body weight, echocardiographic left ventricular mass, and left ventricular end-diastolic diameter and end-diastolic pressure was found. In rats with pressure overload, SIM treatment significantly reduced Ras membrane targeting, Ras in vivo activation, ERK2 phosphorylation, and the ratio cdk4/p27kip1. Conclusions - HMG CoA inhibitor SIM inhibits in vivo Ras signaling and prevents left ventricular hypertrophy development in aortic-banded animals.
AB - Background - Patients with cardiac hypertrophy are at increased cardiovascular risk. It has been hypothesized that hydroxymethylglutaryl coenzyme A reductase inhibitors may exert beneficial effects other than their cholesterol-lowering actions. The aims of the study were to assess the in vivo effects of simvastatin (SIM) on cardiac hypertrophy and on Ras signaling in rats with ascending aorta banding. Methods and Results - Wistar rats were randomized to receive either treatment with SIM or placebo, and then short-term (group I) and long-term (group II) left ventricular pressure overload was performed by placing a tantalum clip on ascending aorta. At the end of treatment period, left and right ventricular weight, body weight, and tibial length were measured and echocardiographic evaluations were performed. Ras signaling was investigated by analyzing Ras membrane localization and activation, ERK2 phosphorylation, and p27kip1 and cdk4 levels. In SIM-treated rats, a significant reduction of left ventricular weight/body weight, echocardiographic left ventricular mass, and left ventricular end-diastolic diameter and end-diastolic pressure was found. In rats with pressure overload, SIM treatment significantly reduced Ras membrane targeting, Ras in vivo activation, ERK2 phosphorylation, and the ratio cdk4/p27kip1. Conclusions - HMG CoA inhibitor SIM inhibits in vivo Ras signaling and prevents left ventricular hypertrophy development in aortic-banded animals.
KW - Hypertrophy
KW - Myocardium
KW - Pressure
KW - Signal transduction
KW - Statins
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U2 - 10.1161/01.CIR.0000034047.70205.97
DO - 10.1161/01.CIR.0000034047.70205.97
M3 - Article
C2 - 12379583
AN - SCOPUS:0037109099
VL - 106
SP - 2118
EP - 2124
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 16
ER -