In Vivo and In Vitro Protective Effects of Pentamethylquercetin on Cardiac Hypertrophy

To investigate the in vivo and in vitro protective effects of pentamethylquercetin (PMQ), a member of polymethoxy flavonoids (PMFs), on cardiac hypertrophy. An in vivo cardiac hypertrophy model established by abdominal aorta banding technique in rats was treated with PMQ in increasing dosages (2.5, 5, and 10 mg center dot kg(-1)center dot d(-1)). An in vitro cardiomyocyte hypertrophy model was induced by treating neonatal cardiomyocytes with endothelin-1 (ET-1, 0.1 mu M). An in vitro fibrosis model was developed in cardiac fibroblasts by aldosterone (Ald, 20 nM) and treated with PMQ (0.3, 1, 3 and 10 mu M). Hemodynamic, morphological, histological, and biochemical changes were evaluated at corresponding time points. The abdominal aorta constriction (AAC) rats demonstrated a significantly elevated blood pressure and profound systolic and diastolic cardiac dysfunction. The resultant cardiac hypertrophy and heart failure were characterized by a significant increase in the heart and lung indices (3.51 +/- 0.30 vs 2.35 +/- 0.24, 5.58 +/- 0.85 vs 3.94 +/- 0.54; both P < 0.01), cardiomyocyte cross-sectional areas (153 +/- 33% vs 100 +/- 5%, P < 0.01) and myocardial fibrosis (9.09 +/- 1.30% vs 1.49 +/- 0.20%, P < 0.01) with concomitant elevation of B-type natriuretic peptide and cardiac collagen mRNA level. Daily oral administration of PMQ (2.5, 5, and 10 mg/kg for 7 weeks) prevented the foregoing histology, gene and protein changes secondary to AAC procedure. In addition, the up-regulated inflammation factors such as TNF-alpha and IL-6, and the down-regulated PPAR alpha and PPAR beta were normalizd by PMQ treatment. PMQ has significant protective effects on cardiac hypertrophy through up-regulating the mRNA and protein levels of PPAR alpha and PPAR beta involved in the process of inflammation response and cardiac fibrosis.