EPIGALLOCATECHIN-3-GALLATE ATTENUATES CARDIAC HYPERTROPHY IN HYPERTENSIVE RATS IN PART BY MODULATION OF MITOGEN-ACTIVATED PROTEIN KINASE SIGNALS

P>It has been demonstrated that epigallocatechin-3-gallate (EGCG) inhibits cardiac hypertrophy through its antihypertensive and anti-oxidant effects. However, the underlying molecular mechanism is not clear. In the present study, we tested the hypothesis that EGCG attenuates transaortic abdominal aortic constriction (TAC)-induced ventricular hypertrophy by regulating mitogen-activated protein kinase (MAPK) signal pathways in hypertensive rats. Four groups of rats were used: (i) a sham-operated control group; (ii) an EGCG-treated (50 mg/kg per day, i.p., for 21 days) sham-operated group; (iii) a TAC group; and (iv) an EGCG-treated TAC group. Histological analysis of whole hearts and biochemical analyses of left ventricular (LV) tissue were used to investigate the effects of EGCG. The results showed that the LV myocyte diameter and the expression of atrial natriuretic peptide, brain natriuretic peptide and beta-myocardial heavy chain were significantly decreased in the EGCG-treated (50 mg/kg per day, i.p.) TAC group. Levels of reactive oxygen species and malondialdehyde in the lV were significantly reduced by EGCG in the TAC group. Total superoxide dismutase, catalase and glutathione peroxidase activities were decreased in the TAC group, and this decrease was significantly restored by EGCG treatment. Phosphorylation of extracellular signal-regulated kinase 2, p38 and c-Jun N-terminal kinase 1 was significantly reversed in the LV of EGCG-treated TAC rats (40%, 53% and 52% vs TAC, respectively), accompanied by significant inhibition of nuclear factor-kappa B and activator protein-1. Transaortic abdominal aortic constriction significantly upregulated LV expression of matrix metalloproteinase-9 from 32 +/- 6 to 100 +/- 12% and this increase was inhibited by EGCG treatment (from 100 +/- 12 to 50 +/- 15%). In addition, TAC decreased mitochondrial DNA copy number and the activity of respiratory chain complexes I (from 100 +/- 7 to 68 +/- 5%), III (from 100 +/- 4 to 2 +/- 5%) and IV (from 766 +/- 2 to 100 +/- 5%); this decrease was reversed by EGCG treatment to levels seen in sham-operated rats. In conclusion, EGCG attenuates TAC-induced ventricular hypertrophy in hypertensive rats in part by suppression of anti-oxidant enzymes and regulation of MAPK signals.