Chen Yintao, Yu Shasha, Zhang Naijin, Li Yuan, Chen Shuang, Chang Ye, Sun Guozhe, Sun Yingxian
Department of Cardiology, The First Hospital of China Medical University, Shenyang, 110001, People's Republic of China.
Biochem Biophys Res Commun. 2017 Apr 29;486(2):423-430. doi: 10.1016/j.bbrc.2017.03.057. Epub 2017 Mar 15.
Previous evidences suggested that atorvastatin not only reduced blood lipids but also reduced myocardial hypertrophy and remodeling. And it was reported that C/EBPβ (CCAAT/enhancer-binding protein β) played a pivotal role both in the physiologic and pathological cardiac hypertrophy. However, it has not been reported before whether this signaling pathway of C/EBPβ participates in protective effect of atorvastatin for hypertrophy cardiomyocytes. In present study, We found that overexpression of C/EBPβ significantly abrogated the effect of atorvastatin on increasing Bcl-2/Bax and PGC-1α while the early and late apoptosis rate increased and mitochondrial membrane potential (MMP) was reduced. In conclusion, we further identified the protective effect of atorvastatin on hypertrophic cardiomyocytes induced by Angiotensin II by rescuing the MMP and inhibiting apoptosis, which might be at least partly attributed to down-regulation of C/EBPβ. And C/EBPβ might be a new target to rescue mitochondrion function and apoptosis in pathological cardiac hypertrophy.
先前的证据表明，阿托伐他汀不仅能降低血脂，还能减轻心肌肥大和重塑。据报道，C/EBPβ（CCAAT/增强子结合蛋白β）在生理性和病理性心肌肥大中均起关键作用。然而，此前尚未有关于C/EBPβ这条信号通路是否参与阿托伐他汀对肥大心肌细胞的保护作用的报道。在本研究中，我们发现C/EBPβ的过表达显著消除了阿托伐他汀对增加Bcl-2/Bax和PGC-1α的作用，同时早期和晚期凋亡率增加，线粒体膜电位（MMP）降低。总之，我们进一步证实了阿托伐他汀通过挽救MMP和抑制凋亡对血管紧张素II诱导的肥大心肌细胞具有保护作用，这可能至少部分归因于C/EBPβ的下调。并且C/EBPβ可能是挽救病理性心肌肥大中线粒体功能和凋亡的新靶点。
