Mechanisms and Optimization Strategies of Paracrine Exosomes from Mesenchymal Stem Cells in Ischemic Heart Disease

Figure 2

Exosomes from different MSCs mediate PCD in myocardial cells after myocardial infarction. MiR-144 and miR-486-5p in exosomes derived from bone marrow mesenchymal stem cells (BMMSC-Exos) and miR-21 in endometrial exosomes derived from mesenchymal stem cells (MSC-Exos) can inhibit apoptosis of hypoxic cardiomyocytes by targeting the PTEN/PI3K/AKT signaling pathway. MiR-21a-5p and miR-25-3p in BMMSC-Exos can reduce the apoptosis of hypoxic cardiomyocytes by downregulating the expression of proapoptotic genes such as FasL, PDPD4, Peli1, and PTEN. MiR-129-5p in BMMSC-Exos inhibits cardiomyocyte apoptosis by regulating the TRAF3/NF-κB signaling pathway. BMMSC-Exos induce autophagy in cardiomyocytes by activating the AMPK/mTOR and AKT/mTOR signaling pathways. Human BMMSC-Exos inhibit pyroptosis by inhibiting the expression of Caspase-1 and NLRP3. Moreover, miR-182-5p in BMMSC-Exos inhibit pyroptosis by inhibiting the expression of GSDMD. MiR-100-5p in exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSC-Exos) inhibit pyroptosis by inhibiting the expression of FOXO3. HUCMSC-Exos reduce ischemic hypoxia-induced iron death in cardiomyocytes by targeting DMT1. LncRNA-UCA1 in human MSC-Exos and Lnc A2M-AS1 in human BMMSC-Exos inhibit myocardial cell apoptosis by adjusting the miR-873-5p/XIAP axis and miR-556-5p/XIAP axis, respectively.