Effect of Atorvastatin on Expression of Peroxisome Proliferator-activated Receptor Beta/delta in Angiotensin II-induced Hypertrophic Myocardial Cells In Vitro.

ABSTRACT

OBJECTIVE: To explore the effect of atorvastatin on cardiac hypertrophy and to determine the potential mechanism involved. METHODS: An in vitro cardiomyocyte hypertrophy from neonatal rats was induced with angiotensin II (Ang II) stimulation. Before Ang II stimulation, the cultured rat cardiac myocytes were pretreated with atorvastatin at different concentrations (0.1, 1, and 10 µmol/L). The following parameters were evaluated the myocyte surface area, 3H-leucine incorporation into myocytes, mRNA expressions of atrial natriuretic peptide, brain natriuretic peptide, matrix metalloproteinase 9, matrix metalloproteinase 2, and interleukin-1ß, mRNA and protein expressions of the δ/ß peroxisome proliferator-activated receptor (PPAR) subtypes. RESULTS: It was shown that atorvastatin could ameliorate Ang II-induced neonatal cardiomyocyte hypertrophy in the area of cardiomyocytes, 3H-leucine incorporation, and the expression of atrial natriuretic peptide and brain natriuretic peptide markedly. Meanwhile, atorvastatin also inhibited the augmented mRNA level of several cytokines in hypertrophic myocytes. Furthermore, the down-regulated expression of PPAR- δ/ß at both the mRNA and protein levels in hypertrophic myocytes could be significantly reversed by atorvastatin treatment. CONCLUSIONS: Atorvastatin could improve Ang II-induced cardiac hypertrophy and inhibit the expression of cytokines. Such effect might be partly achieved through activation of the PPAR-δ/ß pathway.