Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
Mol Med Rep. 2019 Apr;19(4):3179-3189. doi: 10.3892/mmr.2019.9953. Epub 2019 Feb 14.
Ethanol has a toxic effect on the heart, resulting in cardiomyocyte damage. Long‑term high intake of ethanol leads to a non‑ischemic dilated cardiomyopathy termed alcoholic cardiomyopathy (ACM). However, the pathogenesis of alcoholic cardiomyopathy remains unclear. The apoptosis of cardiomyocytes serves an important role in the pathogenesis of ACM. X‑linked inhibitor of apoptosis protein (XIAP) is an important anti‑apoptotic protein in human tissue cells. To the best of our knowledge, no studies have reported on its function in ethanol‑induced cardiomyopathy. Previous works have screened the ACM‑associated differentially expressed microRNAs (miRs), including miR‑186‑5p and miR‑488‑3p. TargetScan bioinformatics software was used to predict 949 target genes associated with miR‑186‑5p, and XIAP was demonstrated to be a target of miR‑186‑5p. The present study firstly analyzed the levels of apoptosis in ethanol‑treated cardiomyocytes using flow cytometry. Alterations in the expression levels of miR‑186‑5p and XIAP were subsequently evaluated in ethanol‑treated AC16 cardiomyocytes to assess the specific molecular mechanisms of ethanol‑induced cardiomyocyte apoptosis. The levels of apoptosis in AC16 cardiomyocytes increased following ethanol treatment, and further increased with the rise in concentration and action time of ethanol. The expression levels of miR‑186‑5p were upregulated, and the expression levels of XIAP were downregulated in ethanol‑treated cardiomyocytes. miR‑186‑5p may regulate ethanol‑induced apoptosis in cardiomyocytes using XIAP as the direct target gene. This study provides a novel therapeutic target for the prevention and treatment of ACM.
乙醇对心脏有毒性作用，导致心肌细胞损伤。长期大量摄入乙醇会导致非缺血性扩张型心肌病，称为酒精性心肌病（ACM）。然而，酒精性心肌病的发病机制尚不清楚。心肌细胞的凋亡在 ACM 的发病机制中起重要作用。凋亡抑制蛋白 X 连锁（XIAP）是人类组织细胞中一种重要的抗凋亡蛋白。据我们所知，目前尚无研究报道其在乙醇诱导的心肌病中的作用。先前的工作已经筛选出与 ACM 相关的差异表达 microRNAs（miRs），包括 miR-186-5p 和 miR-488-3p。TargetScan 生物信息学软件用于预测与 miR-186-5p 相关的 949 个靶基因，结果显示 XIAP 是 miR-186-5p 的靶基因。本研究首次使用流式细胞术分析了乙醇处理的心肌细胞中的凋亡水平。随后评估了乙醇处理的 AC16 心肌细胞中 miR-186-5p 和 XIAP 的表达水平，以评估乙醇诱导心肌细胞凋亡的特定分子机制。乙醇处理后 AC16 心肌细胞的凋亡水平增加，且随着乙醇浓度和作用时间的升高而进一步增加。乙醇处理的心肌细胞中 miR-186-5p 的表达上调，XIAP 的表达下调。miR-186-5p 可能通过 XIAP 作为直接靶基因来调节乙醇诱导的心肌细胞凋亡。本研究为 ACM 的预防和治疗提供了新的治疗靶点。
