The role of "glycolysis-uncoupling of glucose oxidation" in the progression of chronic cardiac hypertroph

Objective　To investigate the roleof"glycolysis-uncoupling of glucose oxidation"in the development of chronic cardiac hypertrophy and its mechanism. Methods　Mouse transaortic-constriction(TAC) model was reproduced to mimic the process of chronic cardiac hypertrophy and development of heart failure.The dynamic expression of phosphorylated pyruvate dehydrogenase(p-PDH)during the progression of chronic cardiac heart failure was analyzed byWestern blotting.Then the effect of dichloroacetate(DCA)-treatment on cardiac function and survival was evaluated. At the same time the cardiocyte apoptosis was compared between the two groups. Results　The p-PDH levels were elevated 1day after TAC, peaking on the 3rd day, and continued to be elevated 14 days after TAC, then significantly lowered 12 weeks after TAC. Compared with control group,the p-PDH expression was significantly down-regulated in DCA-treatment group(P<0.05).Echocardiography showed that DCA-treatment during TAC contributed to the dysfunction of chronic cardiac hypertrophy. TUNEL analysis showed that the apoptotic index in the DCA-treatment group(29.3±2.5)was significantly higher than that in control group(18.8±1.9,P<0.05). Conclusions　Enforced coupling between cytosolic glycolysis and mitochondrial oxidative phosphorylation via DCA acutely contributes to the dysfunction of chronic cardiac hypertrophy in pressure-overloaded heart. The mechanism is possibly associated with an increase incardiocyte apoptosis.