OBJECTIVETo investigate the effect of atorvastatin on cardiac remodeling and function after acute myocardial infarction (AMI) in rats and whether this effect is mediated by transforming growth factor-β1 (TGF-β1) signaling pathway.

METHODSAMI was induced by left coronary artery ligation in 64 male Sprague-Dawley rats, and 45 surviving rats were randomized into control group (n=15), low-dose atorvastatin group (10 mg/kg, n=15) and high-dose atorvastatin group (20 mg/kg, n=15). Similar surgical procedure was performed in sham-operated rats (n=15) without coronary ligation. Atorvastatin was given daily by gavage from the first day after AMI. Eight weeks later, the cardiac function, left ventricular weight/body mass index (LVMI), collagen volume fraction (CVF), and the expressions of TGF-β1 and Smad2 were compared between the groups.

RESULTSAMI caused significantly reduced cardiac function, increased LVMI and CVF, and upregulated expressions of TGF-β1 and Smad2 mRNA and proteins in the control group (P<0.05). The cardiac function, LVMI, and CVF were improved by atorvastatin, which also down-regulated the expressions of TGF-β1 and Smad2 (P<0.05), and the effects were more prominent in high-dose atorvastatin group (P<0.05).

CONCLUSIONAtorvastatin can dose-dependently improve cardiac remodeling and function after AMI in rats, which is mediated by regulating the activity of TGF-β1/Smad2 signaling pathway.

Animals ; Atorvastatin Calcium ; Heart ; drug effects ; physiopathology ; Heptanoic Acids ; pharmacology ; Male ; Myocardial Infarction ; physiopathology ; Pyrroles ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Smad2 Protein ; metabolism ; Transforming Growth Factor beta1 ; metabolism ; Ventricular Remodeling ; drug effects