title: Exosomal transfer of miR-30a between cardiomyocytes regulates autophagy after hypoxia.
abstract: 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.
authors: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430022, China.
authors: Yan
authors: Y
authors: Yang
authors: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430022, China.
authors: Yingying
authors: Y
authors: Li
authors: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430022, China.
authors: Xiao
authors: X
authors: Chen
authors: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430022, China.
authors: Xiang
authors: X
authors: Cheng
authors: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430022, China. liaoyh27@163.com.
authors: Yuhua
authors: Y
authors: Liao
authors: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430022, China. tjyuxian@hotmail.com.
authors: Xian
authors: X
authors: Yu
mesh_terms: D000328:Adult; D000368:Aged; D001343:Autophagy / Q000235:genetics; D000071192:Autophagy-Related Protein 12 / Q000235:genetics / Q000378:metabolism; D000071186:Beclin-1 / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia; D002460:Cell Line; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D000860:Hypoxia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D020320:Oligoribonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D019899:Paracrine Communication; D015398:Signal Transduction
chemical_list: C466624:ATG12 protein, human; D000071192:Autophagy-Related Protein 12; C491997:BECN1 protein, human; D000071186:Beclin-1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C477012:MAP1LC3A protein, human; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; D020320:Oligoribonucleotides, Antisense
keywords: Autophagy; Cardiomyocytes; Exosomes; Hypoxia; miR-30a