尼可地尔
核仁素
自噬
标记法
细胞凋亡
心肌纤维化
内科学
心脏纤维化
医学
纤维化
化学
细胞生物学
生物
生物化学
核仁
细胞质
作者
Honghui Deng,Jian Zou,Nian Wang,Heng Ma,Lili Zhu,Liu Ke,Mei‐Dong Liu,Kangkai Wang,Xianzhong Xiao
标识
DOI:10.1016/j.cellsig.2022.110272
摘要
The present study aimed to investigate whether the drug nicorandil can improve cardiac remodeling after myocardial infarction (MI) and the underlying mechanisms.Mouse MI was established by the ligation of the left anterior descending coronary artery and H9C2 cells were cultured to investigate the underlying molecular mechanisms. The degree of myocardial collagen (Col) deposition was evaluated by Masson's staining. The expressions of nucleolin, autophagy and myocardial remodeling-associated genes were measured by Western blotting, qPCR, and immunofluorescence. The apoptosis of myocardial tissue cells and H9C2 cells were detected by TUNEL staining and flow cytometry, respectively. Autophagosomes were observed by transmission electron microscopy.Treatment with nicorandil mitigated left ventricular enlargement, improved the capacity of myocardial diastolic-contractility, decreased cardiomyocyte apoptosis, and inhibited myocardial fibrosis development post-MI. Nicorandil up-regulated the expression of nucleolin, promoted autophagic flux, and decreased the expressions of TGF-β1 and phosphorylated Smad2/3, while enhanced the expression of BMP-7 and phosphorylated Smad1 in myocardium. Nicorandil decreased apoptosis and promoted autophagic flux in H2O2-treated H9C2 cells. Autophagy inhibitors 3-methyladenine (3MA) and chloroquine diphosphate salt (CDS) alleviated the effects of nicorandil on apoptosis. Knockdown of nucleolin decreased the effects of nicorandil on apoptosis and nicorandil-promoted autophagic flux of cardiomyocytes treated with H2O2.Treatment with nicorandil alleviated myocardial remodeling post-MI through up-regulating the expression of nucleolin, and subsequently promoting autophagy, followed by regulating TGF-β/Smad signaling pathway.
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