Involvement of phosphatase and tensin homolog-induced putative kinase 1/Parkin-mediated autophagy in angiotensin II-induced cardiac hypertrophy in C57BL/6 mice
Involvement of phosphatase and tensin homolog-induced putative kinase 1/Parkin-mediated autophagy in angiotensin II-induced cardiac hypertrophy in C57BL/6 mice
复制标题
磷酸酶和张力蛋白同系物诱导的推定激酶 1/Parkin 介导的自噬参与血管紧张素 II 诱导的 C57BL/6 小鼠心脏肥大
DOI：
10.1177/0300060519896143
复制
发表时间：
2019-12-31
影响因子：
1.6
通讯作者：
Wei, Jin
中科院分区：
文献类型：
--
作者：
Fan, Gang;Chen, Meng-Jie;Wei, Jin
目的研究自噬在血管紧张素II（angiotensin II，Ang II）诱导的C57 BL/6小鼠心肌肥厚中的作用。Ang Ⅱ组小鼠腹腔注射Ang Ⅱ（3 mg/kg/d）。观察心脏结构、心肌病理改变、线粒体结构、自噬体、线粒体膜电位（MMP）和心肌细胞凋亡。检测磷酸酶和张力蛋白同源物（PTEN）诱导的推定激酶1（PINK 1）、Parkin和微管相关蛋白1A/1B-轻链3（LC 3）II的蛋白表达水平以及心钠素（ANP）和脑钠素（BNP）的mRNA表达。与对照组相比，Ang II组ANP和BNP mRNA水平以及PINK 1、Parkin和LC 3 II蛋白水平均显著升高。Ang Ⅱ组MMP和左室射血分数明显低于对照组。结论PINK 1/PARKIN介导的自噬通过影响心肌细胞凋亡和线粒体功能参与了Ang II诱导的心肌肥大。
ObjectiveTo study the role of autophagy in angiotensin II-induced cardiac hypertrophy in C57BL/6 mice.MethodsWe randomly assigned 10 C57BL/6 mice into the control and angiotensin II (Ang II) groups (n = 5 in each group). Ang II group mice were injected with Ang II (3 mg/kg/day). Cardiac structure, myocardial pathological changes, mitochondrial structure, autophagosomes, mitochondrial membrane potential (MMP), and myocardial apoptosis were examined. Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1), Parkin, and microtubule-associated protein1A/1B-light chain 3 (LC3) II protein expression levels and mRNA expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were examined.ResultsThe heart weight/body weight ratio, posterior wall of the left ventricle, myocardial apoptosis (%), relative number of autophagosomes, ANP and BNP mRNA levels, and PINK1, Parkin, and LC3 II protein levels were significantly higher in the Ang II group than in the control group. The MMP and left ventricular ejection fraction were significantly lower in the Ang II group than in the control group. There was disordered arrangement of cardiomyocytes and mitochondria, and obvious mitochondrial swelling, cardiomyocyte hypertrophy, and fibrosis in the Ang II group.ConclusionPINK1/PARKIN-mediated autophagy is involved in Ang II-induced cardiac hypertrophy by affecting myocardial apoptosis and mitochondrial function.