Department of Emergency, Zhejiang Hospital, Hangzhou, Zhejiang, China.
Department of Cardiology, Zhuji People's Hospital of Zhejiang Province, Zhuji, Zhejiang, China.
Bioengineered. 2021 Dec;12(1):8897-8907. doi: 10.1080/21655979.2021.1988368.
Cardiomyocyte apoptosis and autophagy play important roles in acute myocardial infarction (AMI), but the effect of leucine-rich alpha-2-glycoprotein 1 (LRG1) on the apoptosis and autophagy of H9c2 has not yet been reported. It was found through differential gene analysis and LASSO analysis that LRG1 was the key gene in AMI. In this study, western blot was applied to detect the protein expression of Bax, Bcl2, LC3, p62, LRG1 and hypoxia-inducible factor-1α (HIF-1α); CCK-8 assay was employed to detect cell viability; Annexin V-FITC/PI staining was adopted to evaluate apoptosis, and immunofluorescence assay was applied to detect autophagy. Under hypoxia conditions in H9c2 cells, LRG1 protein levels were increased, the cell activity was decreased, and apoptosis and autophagy were promoted; the downregulated LRG1 significantly enhanced cell viability but inhibited apoptosis and autophagy. When knocking down HIF-1α in the overexpressed LRG1 cells, the effects of LRG1 were reversed under hypoxia condition. In conclusion, LRG1/HIF-1α promoted H9c2 cell apoptosis and autophagy in hypoxia, potentially providing new ideas for the determination and treatment of AMI. LRG1: Leucine-rich alpha-2-glycoprotein 1; LRR: leucine-rich repeat; HIF-1α: Hypoxia-inducible factor-1α; AMI: acute myocardial infarction.
心肌细胞凋亡和自噬在急性心肌梗死（AMI）中发挥重要作用，但亮氨酸丰富的α-2-糖蛋白 1（LRG1）对 H9c2 细胞凋亡和自噬的影响尚未报道。通过差异基因分析和 LASSO 分析发现，LRG1 是 AMI 的关键基因。在本研究中，采用 Western blot 检测 Bax、Bcl2、LC3、p62、LRG1 和缺氧诱导因子-1α（HIF-1α）的蛋白表达；采用 CCK-8 法检测细胞活力；采用 Annexin V-FITC/PI 染色评估细胞凋亡，采用免疫荧光法检测自噬。在 H9c2 细胞缺氧条件下，LRG1 蛋白水平升高，细胞活性降低，促进细胞凋亡和自噬；下调 LRG1 可显著增强细胞活力，但抑制细胞凋亡和自噬。当在过表达 LRG1 的细胞中敲低 HIF-1α 时，LRG1 的作用在缺氧条件下被逆转。总之，LRG1/HIF-1α 促进 H9c2 细胞在缺氧条件下的凋亡和自噬，可能为 AMI 的确定和治疗提供新的思路。LRG1：亮氨酸丰富的α-2-糖蛋白 1；LRR：亮氨酸丰富重复；HIF-1α：缺氧诱导因子-1α；AMI：急性心肌梗死。
