Ji Xiao-Bing, Li Xiu-Rong, Sun Qi, Zhou Yang, Wen Ping, Dai Chun-Sun, Yang Jun-Wei
Center for Kidney Disease, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Cell Physiol Biochem. 2015;36(5):1688-98. doi: 10.1159/000430142. Epub 2015 Jul 13.
Uncoupling protein 2 (UCP2) is critical in regulating energy metabolism. Due to the significant change in energy metabolism of myocardium upon pressure overload, we hypothesize that UCP2 could contribute to the etiology of cardiac hypertrophy.
Adult male C57BL/6J mice were subjected to pressure overload by using transverse aortic constriction (TAC), and then received genipin (a UCP2 selective inhibitor; 25 mg/kg/d, ip) or vehicle for three weeks prior to histologic assessment of myocardial hypertrophy. ATP concentration, ROS level, and myocardial apoptosis were also examined. A parallel set of experiments was also conducted in UCP2-/- mice.
TAC induced left ventricular hypertrophy, as reflected by increased ventricular weight/thickness and increased size of myocardial cell (vs. sham controls). ATP concentration was decreased; ROS level was increased. Apoptosis and fibrosis markers were increased. TAC increased mitochondrial UCP2 expression in the myocardium at both mRNA and protein levels. Genipin treatment attenuated cardiac hypertrophy and the histologic/biochemical changes described above. Hypertrophy and associated changes induced by TAC in UCP2-/- mice were much less pronounced than in WT mice.
Blocking UCP2 expression attenuates cardiac hypertrophy induced by pressure overload.
解偶联蛋白2（UCP2）在调节能量代谢中起关键作用。由于压力过载时心肌能量代谢会发生显著变化，我们推测UCP2可能与心脏肥大的病因有关。
成年雄性C57BL/6J小鼠通过横向主动脉缩窄（TAC）造成压力过载，然后在对心肌肥大进行组织学评估前3周，给予京尼平（一种UCP2选择性抑制剂；25mg/kg/d，腹腔注射）或赋形剂。同时检测ATP浓度、活性氧水平和心肌细胞凋亡情况。在UCP2基因敲除小鼠中也进行了一组平行实验。
TAC诱导左心室肥大，表现为心室重量/厚度增加和心肌细胞大小增大（与假手术对照组相比）。ATP浓度降低；活性氧水平升高。凋亡和纤维化标志物增加。TAC使心肌中线粒体UCP2在mRNA和蛋白质水平的表达均增加。京尼平治疗减轻了心脏肥大以及上述组织学/生化变化。TAC在UCP2基因敲除小鼠中诱导的肥大及相关变化比野生型小鼠明显减轻。
阻断UCP2表达可减轻压力过载诱导的心脏肥大。
