Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Int J Cardiol. 2024 Nov 1;414:132395. doi: 10.1016/j.ijcard.2024.132395. Epub 2024 Jul 27.
After acute myocardial infarction (AMI), intercellular communication is crucial for maintaining cardiac homeostasis and patient survival. Exosomes secreted by cardiomyocytes serve as carriers for transporting microRNA(miRNAs), participating in intercellular signaling and the regulation of cardiac function. This study aims to investigate the role of exosomal microRNA-30a(miR-30a) during AMI and its underlying mechanisms. AMI was induced by permanent ligation of the left anterior descending (LAD) artery in C57BL/6 mice. The expression of miR-30a in mice was respectively enhanced and inhibited by administering agomiR-30a and antagomiR-30a. Using HL-1 cardiomyocytes and RAW264.7 macrophages for in vitro experiments, HL-1 cardiomyocytes were cultured under hypoxic conditions to induce ischemic injury. Following isolation and injection of exosomals, a variety of validation methods were utilized to assess the expression of miR-30a, and investigate the effects of enriched exosomal miR-30a on the state of cardiomyocytes. After AMI, the level of exosomal miR-30a in the serum of mice significantly increased and was highly enriched in cardiac tissue. Cardiomyocytes treated with agomiR-30a and miR-30a-enriched exosomes exhibited inhibition of cell autophagy, increased cell apoptosis, mice showed an larger myocardial infarct area and poorer cardiac function. Exosomes released from hypoxic cardiomyocytes transferred miR-30a to cardiac resident macrophages, promoting the polarization into pro-inflammatory M1 macrophages. In conclusion, murine exosomal miR-30a exacerbates cardiac dysfunction post-AMI by disrupting the autophagy-apoptosis balance in cardiomyocytes and polarizing cardiac resident macrophages into pro-inflammatory M1 macrophages. Modulating the expression of miR-30a may reduce cardiac damage following AMI, and targeting exosomal miR-30a could be a potential therapeutic approach for AMI.
急性心肌梗死（AMI）后，细胞间通讯对于维持心脏内环境稳定和患者生存至关重要。心肌细胞分泌的外泌体作为携带 microRNA（miRNAs）的载体，参与细胞间信号传递和心脏功能的调节。本研究旨在探讨外泌体 microRNA-30a（miR-30a）在 AMI 中的作用及其潜在机制。通过结扎左前降支（LAD）动脉诱导 C57BL/6 小鼠 AMI。通过给予 agomiR-30a 和 antagomiR-30a 分别增强和抑制小鼠 miR-30a 的表达。在 HL-1 心肌细胞和 RAW264.7 巨噬细胞的体外实验中，将 HL-1 心肌细胞置于缺氧条件下培养以诱导缺血损伤。分离并注射外泌体后，采用多种验证方法评估 miR-30a 的表达，并研究富含 exosomal miR-30a 对心肌细胞状态的影响。AMI 后，小鼠血清中外泌体 miR-30a 的水平显著升高，并在心脏组织中高度富集。用 agomiR-30a 处理的心肌细胞和富含 miR-30a 的外泌体处理的心肌细胞中，细胞自噬受到抑制，细胞凋亡增加，小鼠心肌梗死面积增大，心功能变差。缺氧心肌细胞释放的外泌体将 miR-30a 转移至心脏驻留巨噬细胞，促进其向促炎 M1 巨噬细胞极化。总之，鼠源性 exosomal miR-30a 通过破坏心肌细胞自噬-凋亡平衡和促进心脏驻留巨噬细胞向促炎 M1 巨噬细胞极化，加剧 AMI 后心功能障碍。调节 miR-30a 的表达可能减轻 AMI 后的心脏损伤，靶向 exosomal miR-30a 可能是 AMI 的一种潜在治疗方法。
