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Exosomes as a messager to regulate the crosstalk between macrophages and cardiomyocytes under hypoxia conditions
Authors:Zenglei Zhang  Yanyan Xu  Chang Cao  Bo Wang  Jiacheng Guo  Zhen Qin  Yongzheng Lu  Jianchao Zhang  Li Zhang  Wei Wang  Jinying Zhang  Junnan Tang
Affiliation:1. Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou China ; 2. Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou China ; 3. Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou Henan, China ; 4. Henan Medical Association, Zhengzhou China
Abstract:Recent studies have confirmed that cardiomyocyte‐derived exosomes have many pivotal biological functions, like influencing the progress of coronary artery disease via modulating macrophage phenotypes. However, the mechanisms underlying the crosstalk between cardiomyocytes and macrophages have not been fully characterized. Hence, this study aimed to observe the interaction between cardiomyocytes under hypoxia and macrophages through exosome communication and further evaluate the ability of exosomes derived from cardiomyocytes cultured under hypoxic conditions (Hypo‐Exo) to polarize macrophages, and the effect of alternatively activated macrophages (M2) on hypoxic cardiomyocytes. Our results revealed that hypoxia facilitated the production of transforming growth factor‐beta (TGF‐β) in H9c2 cell‐derived exosomes. Moreover, exosomes derived from cardiomyocytes cultured under normal conditions (Nor‐Exo) and Hypo‐Exo could induce RAW264.7 cells into classically activated macrophages (M1) and M2 macrophages respectively. Likewise, macrophage activation was induced by circulating exosomes isolated from normal human controls (hNor‐Exo) or patients with acute myocardial infarction (hAMI‐Exo). Thus, our findings support that the profiles of hAMI‐Exo have been changed, which could regulate the polarization of macrophages and subsequently the polarized M2 macrophages reduced the apoptosis of cardiomyocytes in return. Based on our findings, we speculate that exosomes have emerged as important inflammatory response modulators regulating cardiac oxidative stress injury.
Keywords:cardiomyocytes, cell‐  cell interactions, exosomes, hypoxia, macrophage polarization
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