Department of Cardiovascular Medicine, Cangzhou Central Hospital , Cangzhou , China.
Nephrology Department, Cangzhou Central Hospital , Cangzhou , China.
Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):3976-3984. doi: 10.1080/21691401.2019.1671432.
MicroRNAs (miRNAs) play a key role in various pathological processes like atrial fibrillation (AF), which is a common cardiac arrhythmia. Exosomes are essential information carrier in the intercellular communication. Therefore, this study aimed to investigate the effects of exosomal miR-320d on cardiomyocytes with AF and related mechanisms. To do this, AMSCs were transfected with miR-320d mimics, AMSCs-derived exosomes were co-cultured with cardiomyocytes with AF. MTT, TUNEL staining, flow cytometry, real-time PCR, western blots, and luciferase reporter assays were performed. The results revealed that miR-320d expression was decreased in AF cardiomyocytes. AF increased apoptosis and reduced cell viability in cardiomyocytes. By transfection with miR-320d mimics, the miR-320d level was increased in AMSCs, exosomes and cardiomyocytes, which reversed the effect of AF on cardiomyocytes. STAT3 was down-regulated in AF cardiomyocytes and was a direct target gene of miR-320d. Inhibition of STAT3 abolished the effect of modified exosomes in cardiomyocytes, causing decreased apoptosis and increased cell viability. Taken together, the results suggested that exosomal miR-320d was associated with AF cardiomyocytes apoptosis and cell viability and that the effect of miR-320d on cardiomyocytes is STAT3-dependent. Therefore, this study provides a novel understanding of the molecular basis of AF and provides insight into therapeutic strategies for AF.
微小 RNA（miRNA）在各种病理过程中发挥着关键作用，如心房颤动（AF），这是一种常见的心律失常。外泌体是细胞间通讯的重要信息载体。因此，本研究旨在探讨外泌体 miR-320d 对 AF 心肌细胞的影响及其相关机制。为此，将 miR-320d 模拟物转染入 AMSCs，将 AMSCs 来源的外泌体与 AF 心肌细胞共培养。进行 MTT、TUNEL 染色、流式细胞术、实时 PCR、western blot 和荧光素酶报告基因检测。结果显示，AF 心肌细胞中 miR-320d 表达降低。AF 增加了心肌细胞的凋亡并降低了细胞活力。通过转染 miR-320d 模拟物，可增加 AMSCs、外泌体和心肌细胞中的 miR-320d 水平，从而逆转 AF 对心肌细胞的影响。AF 心肌细胞中 STAT3 下调，是 miR-320d 的直接靶基因。抑制 STAT3 可消除修饰后的外泌体对心肌细胞的作用，导致凋亡减少和细胞活力增加。综上所述，结果表明外泌体 miR-320d 与 AF 心肌细胞凋亡和细胞活力有关，miR-320d 对心肌细胞的作用依赖于 STAT3。因此，本研究为 AF 的分子基础提供了新的认识，并为 AF 的治疗策略提供了思路。
