米贝夫拉地尔
PI3K/AKT/mTOR通路
蛋白激酶B
自噬
利钠肽
脑利钠肽
肌肉肥大
心钠素
内科学
心力衰竭
医学
内分泌学
化学
药理学
细胞凋亡
钙通道
信号转导
钙
生物化学
作者
Ling-Gong Zhao,Peilin Li,Ying Dai,Jiajie Deng,Meng-ya Shan,Bin Chen,Kebin Zhang,Shaodong Guo,Zihui Xu
出处
期刊:Journal of Cardiovascular Pharmacology
[Ovid Technologies (Wolters Kluwer)]
日期:2020-05-20
卷期号:76 (2): 246-254
被引量:13
标识
DOI:10.1097/fjc.0000000000000844
摘要
Abstract: Cardiac hypertrophy causes heart failure and is associated with hyperglycemia in patients with diabetes mellitus. Mibefradil, which acts as a T-type calcium channel blocker, exerts beneficial effects in patients with heart failure. In this study, we explored the effects and mechanism of mibefradil on high-glucose–induced cardiac hypertrophy in H9c2 cells. H9c2 cells were incubated in a high-glucose medium and then treated with different concentrations of mibefradil in the presence or absence of the Akt inhibitor MK2206 or mTOR inhibitor rapamycin. Cell size was evaluated through immunofluorescence, and mRNA expression of cardiac hypertrophy markers (atrial natriuretic peptide, brain natriuretic peptide, and β-myosin heavy chain) was assessed by using quantitative real-time polymerase chain reaction. Changes in the expression of p-PI3K, p-Akt, and p-mTOR were evaluated using Western blotting, and autophagosome formation was detected using transmission electron microscopy. Our results indicate that mibefradil reduced the size of H9c2 cells, decreased mRNA expression of atrial natriuretic peptide, brain natriuretic peptide, and β-myosin heavy chain, and decreased the level of autophagic flux. However, MK2206 and rapamycin induced autophagy and reversed the effects of mibefradil on high-glucose–induced H9c2 cells. In conclusion, mibefradil ameliorated high-glucose–induced cardiac hypertrophy by activating the PI3K/Akt/mTOR pathway and inhibiting excessive autophagy. Our study shows that mibefradil can be used therapeutically to ameliorate cardiac hypertrophy in patients with diabetes mellitus.
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