心脏成纤维细胞向肌成纤维细胞表型分化是高血压心肌纤维化的关键步骤。分化过程中偶联着代谢模式从氧化磷酸化向糖酵解的转变，然而，心脏成纤维细胞如何启动代谢流变化的内在机制尚不清楚。近期，我们发现血管紧张素II诱导心脏成纤维细胞分化过程中，伴随Sirtuin3（SIRT3）表达降低，与线粒体丙酮酸转运体2（mitochondrial pyruvate transport 2，MPC2）的高乙酰化水平相关联。推测MPC2乙酰化修饰通过减少丙酮酸转运，驱动代谢模式的转变参与激活心脏成纤维细胞。因此，本项目以成纤维细胞能量代谢模式为切入点，研究SIRT3调节MPC2的乙酰化修饰对丙酮酸转运及糖酵解的影响；MPC2的乙酰化修饰促进心脏成纤维细胞表型分化；成纤维细胞通过“乳酸梭”参与心肌细胞能量代谢。阐明SIRT3/MPC2-代谢重塑-心肌纤维化之间的关系，为逆转心肌重构开辟新的思路。

Differentiation of cardiac fibroblasts into myofibroblasts is responsible for connective tissue build-up in hypertensive myocardial remodeling. During this conversion, cell metabolism undergoes a shift from oxidative phosphorylation to aerobic glycolysis. The underlying regulators of the metabolic program in Angiotension II (Ang II)-induced differentiation of cardiac fibroblasts into myofibroblasts remain unclear. Recently, we found the expression of SIRT3 was decreased in cardiac fibroblasts, accompanied with accumulation of glycolysis products and elevation of acetylation level of mitochondrial pyruvate transport 2 (MPC2). It is speculated that MPC2 acetylation is involved in the activation of cardiac fibroblasts by reducing pyruvate transport and driving the transformation of metabolic patterns. Therefore, this project is to investigate the effect of SIRT3 on the regulation of acetylation of MPC2 on pyruvate transport and glycolysis; SIRT3 regulates the activity of MPC2 to promote phenotypic differentiation of cardiac fibroblasts，and activated fibroblasts alter cardiomyocyte function by glycolysis-products. This study would clarify the relationship among SIRT3/MPC2, metabolic reprogramming and cardiac fibrosis. Taken together, these findings may provide a potential target for treatment hypertensive myocardial fibrosis.