The Effects of Atorvastatin on Left Ventricular Remodeling in Spontaneously Hypertensive Rats

Background Abnormal cardiomyocyte apoptosis and myocardial connective tissue growth factor(CTGF) expression were involved in the development of left ventricular remodeling in hypertension.Statins administration improved left ventricular remodeling in spontaneously hypertensive rats(SHR),but the mechanisms are not clear.Objective To investigate the effects of atorvastatin administered in the early stage on left ventricular remodeling in SHR,and to explore the underlying mechanisms involved.Methods Sixteen male SHR were randomized to receive distilled water(placebo) or atorvastatin [50 mg/(kg·d) SHR-ATV] for 12 weeks.The age matched male Wistar-Kyoto rats(WKY) were gavaged with distilled water as control.Left ventricular remodeling was evaluated by determination of the ratio of left ventricular weight to body weight,cardiomyocyte diameter and interstitial fibrosis.Myocardium CTGF expression level was examined with Western blot,and cardiomyocyte apoptosis with TUNEL method.Results Compared with WKY and placebo,atorvastatin treatment significantly decreased serum TC,TG,LDL-C levels and systolic blood pressure in SHR;atorvastatin significantly inhibited left ventricular remodeling,decreased the ratio of left ventricular weight to body weight [(4.0±0.4) vs(4.7±0.4) mg/g,P0.05],cardiomyocyte diameter [(16.2±2.8) vs(19.0±1.0) μm,P0.05] and interstitial fibrosis [(3.3±2.1)% vs(4.5±1.8)%,P0.05].Atorvastatin seems to have modulating effect in myocardial CTGF and apoptosis manifested by preventing the increases in CTGF,while accentuating the cells apoptosis ratio in placebo SHR[SHR-ATV:(5.2±0.6)% vs placebo:(1.9±0.3)%,P0.05].ConclusionAtorvastatin administered in the early stage effectively pervented left ventricular remodeling in SHR by inhibiting myocardium CTGF expression and inducing cardiomyocyte apoptosis.