Ischemia/hypoxia inhibits cardiomyocyte autophagy and promotes apoptosis via the Egr-1/Bim/Beclin-1 pathway

• 作者: Bo SU Jing ZHENG Lang LI Man-Yun LONG Wen-Hao WU Xian-Tao WANG Yu-Han SUN
• 来源期刊: 老年心脏病学杂志（英文版）
• 年，卷（期）: 2020,（5）
• 页码范围: 284-293
• 页数: 10页
• 语种: 英文
• DOI: 10.11909/j.issn.1671-5411.2020.05.004

摘要

Background Myocardial injury caused by microvascular obstruction (MVO) is characterized by persistent ischemia/hypoxia (IH) of cardiomyocytes after microembolization.Autophagy and Egr-1 were closely associated with various cardiovascular diseases,including MVO.Bim and Beclin-1 are the important genes for autophagy and apoptosis.We aimed to explore whether the Egr-1/Bim/Beclin-1 pathway is involved in regulating autophagy and apoptosis in IH-exposed cardiomyocytes.Methods Neonatal rat cardiomyocytes exposed to the IH environment in vitro were transfected with lentivirus expressing Egr-1 or Egr-1 shRNA,or further treated with 3-methyladenine (3-MA).The expressions of autophagy and apoptosis-associated genes were evaluated using RT-qPCR and Western blots assays.Autophagic vacuoles and autophagic flux were detected by transmission electron microscopy (TEM) and confocal microscope,respectively.Cell injury was assessed by lactate dehydrogenase (LDH) leakage,and apoptosis was determined by flow cytometry.Results IH exposure elevated Egr-1 and Bim expressions,and decreased Beclin-1 expression in rat cardiomyocytes.Egr-1 overexpression in IH-exposed cardiomyocytes significantly up-regulated the levels of Egr-1 and Bim,and down-regulated the level of Beclin-1.Egr-1 knockdown resulted in down-regulated expressions of Egr-1 and Bim,as well as up-regulated expression of Beclin-1.In addition,Egr-1 knockdown induced autophagy was suppressed by 3-MA treatments.TEM and autophagic flux experiments also confirmed that Egr-1 inhibited autophagy progression in IH-exposed cardiomyocytes.Egr-1 suppression protected cardiomyocytes from IH-induced injury,as evidenced by the positive correlations between Egr-1 expression and LDH leakage or apoptosis index in IH-exposed cardiomyocytes.Conclusions IH-induced cardiomyocyte autophagy and apoptosis are regulated by the Egr-1/Bim/Beclin-1 pathway,which is a potential target fortreating cardiomyocyte injury caused by MVO in the IH environment.