Yang Yan, Li Yingying, Chen Xiao, Cheng Xiang, Liao Yuhua, Yu Xian
Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430022, China.
J Mol Med (Berl). 2016 Jun;94(6):711-24. doi: 10.1007/s00109-016-1387-2. Epub 2016 Feb 9.
Recent studies have indicated a protective role of physiological autophagy in ischemic heart disease. However, the underlying mechanisms of autophagy regulation after ischemia are poorly understood. Exosomes are nano-sized vesicles released from cells that play critical roles in mediating cell-to-cell communication through the transfer of microRNAs. In this study, we observed that miR-30a was highly enriched in exosomes from the serum of acute myocardial infarction (AMI) patients in vivo and culture medium of cardiomyocytes after hypoxic stimulation in vitro. We also found that hypoxia inducible factor (HIF)-1α regulates miR-30a, which efficiently transferred via exosomes between cardiomyocytes after hypoxia. Inhibition of miR-30a or release of exosomes increased the expression of the core autophagy regulators beclin-1, Atg12, and LC3II/LC3I, which contributed to maintaining the autophagic response in cardiomyocytes after hypoxia. Taken together, the present study showed that exosomes from hypoxic cardiomyocytes regulate autophagy by transferring miR-30a in a paracrine manner, which revealed a new pathway of autophagy regulation that might comprise a promising strategy to treat ischemic heart disease.
miR-30a is highly enriched in exosomes from the serum of AMI patients. Hypoxia induces miR-30a upregulation and enrichment into exosomes. MiR-30a is efficiently transferred via exosomes between hypoxic cardiomyocytes. Inhibition of exosome release contributes to maintaining of autophagy after hypoxia. Inhibition of miR-30a augments autophagy after hypoxia.
最近的研究表明生理性自噬在缺血性心脏病中具有保护作用。然而，缺血后自噬调节的潜在机制仍知之甚少。外泌体是细胞释放的纳米级囊泡，通过微小RNA的转移在介导细胞间通讯中发挥关键作用。在本研究中，我们观察到miR-30a在急性心肌梗死（AMI）患者血清来源的体内外泌体以及体外缺氧刺激后的心肌细胞培养基中高度富集。我们还发现缺氧诱导因子（HIF）-1α调节miR-30a，缺氧后miR-30a通过外泌体在心肌细胞之间有效转移。抑制miR-30a或外泌体释放会增加核心自噬调节因子beclin-1、Atg12和LC3II/LC3I的表达，这有助于维持缺氧后心肌细胞中的自噬反应。综上所述，本研究表明缺氧心肌细胞来源的外泌体通过旁分泌方式转移miR-30a来调节自噬，这揭示了一种新的自噬调节途径，可能为治疗缺血性心脏病提供一种有前景的策略。
miR-30a在AMI患者血清来源的外泌体中高度富集。缺氧诱导miR-30a上调并富集到外泌体中。miR-30a通过外泌体在缺氧心肌细胞之间有效转移。抑制外泌体释放有助于维持缺氧后的自噬。抑制miR-30a可增强缺氧后的自噬。
