title: Hydroxymethylglutaryl coenzyme A reductase inhibitor simvastatin prevents cardiac hypertrophy induced by pressure overload and inhibits p21ras activation.
abstract: 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.
  
  
  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 p27(kip1) 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/p27(kip1).
  
  
  CONCLUSIONS
  HMG CoA inhibitor SIM inhibits in vivo Ras signaling and prevents left ventricular hypertrophy development in aortic-banded animals.
authors.affiliation: Division of Cardiology, Magna Graecia University, Catanzaro, Italy. indolfi@unicz.it
authors.forename: Ciro
authors.initials: C
authors.lastname: Indolfi
authors.forename: Emilio
authors.initials: E
authors.lastname: Di Lorenzo
authors.forename: Cinzia
authors.initials: C
authors.lastname: Perrino
authors.forename: Angela Maria
authors.initials: AM
authors.lastname: Stingone
authors.forename: Antonio
authors.initials: A
authors.lastname: Curcio
authors.forename: Daniele
authors.initials: D
authors.lastname: Torella
authors.forename: Antonello
authors.initials: A
authors.lastname: Cittadini
authors.forename: Luca
authors.initials: L
authors.lastname: Cardone
authors.forename: Carmela
authors.initials: C
authors.lastname: Coppola
authors.forename: Luigi
authors.initials: L
authors.lastname: Cavuto
authors.forename: Oreste
authors.initials: O
authors.lastname: Arcucci
authors.forename: Luigi
authors.initials: L
authors.lastname: Sacca
authors.forename: Enrico Vittorio
authors.initials: EV
authors.lastname: Avvedimento
authors.forename: Massimo
authors.initials: M
authors.lastname: Chiariello
mesh_terms: D000818:Animals; D004452:Echocardiography; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D016283:Proto-Oncogene Proteins p21(ras) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D017725:Ventricular Pressure
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D020928:Mitogen-Activated Protein Kinases; D016283:Proto-Oncogene Proteins p21(ras)