Exosomes from adipose-derived stem cells alleviate myocardial infarction via microRNA-31/FIH1/HIF-1α pathway

Abstract

Please cite this article as: D. Zhu, Y. Wang, M. Thomas, et al., Exosomes from adiposederived stem cells alleviate myocardial infarction via microRNA-31/FIH1/HIF-1α pathway,

From cerebral ischemia towards myocardial, renal, and hepatic ischemia: Exosomal miRNAs as a general concept of intercellular communication in ischemia-reperfusion injury

“… 106 , 107 Exosomes, in the meantime, could be taken up by neighboring or distant myocardial cells, given their various targets, which they modulate by posttranscriptional regulation of gene expression; miRNAs loaded into exosomes are potent repair factors. 108 There is increasing evidence that miRNAs are selectively enriched in exosomes, exerting biological functions via modulating specific aspects of myocardial ischemia and, as such, participating in cardiomyocyte survival, cardiac functional recovery, inflammatory responses, and angiogenesis, 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 as indicated in Table 2 and Figure 4 and further discussed in the following sections.…”

“…As such, a series of miRNAs were shuttled via exosomes, including miR-21, miR-98-5p, miR-25, miR-30e, miR-125b, miR-126, miR-4732-3p, miR-146a, miR-185, miR-150-5p, miR-210, miR-212-5p, miR-31, miR-486-5p, miR-338, and miR-671, which, collected from MSCs, cardiac progenitor cells, endothelial cells, endothelial progenitor cells, or patient serum, promoted cardiomyocyte survival by downregulating miRNA targets including PDCD4, FASL, TLR4, PTEN, LOX1, p53, BAK, or SOCS2. 112 , 114 , 117 , 118 , 120 , 123 , 124 , 127 , 129 , 130 , 131 , 132 , 133 , 137 , 138 , 140 , 141 , 142 In addition to the effect on cardiomyocyte survival, several miRNAs, namely miR-24, miR-98-5p, miR-125b, miR-126, miR-133a-3p, miR-150-5p, miR-338, miR-4732-3p, miR-31, miR-210, and miR-486-5p, loading into exosomes from cardiomyocytes, MSCs, or endothelial cells were identified to promote cardiac function recovery by promoting cardiomyocyte survival, anti-inflammation, angiogenesis, or anti-fibrosis. 114 , 117 , 118 , 120 , 124 , 127 , 131 , 138 , 141 , 142 Suggestively, exosomal miRNAs play momentous roles in coordinating responses to cardioprotective effects, i.e., by promoting cardiomyocyte survival and cardiac functional recovery.…”

“… 112 , 114 , 117 , 118 , 120 , 123 , 124 , 127 , 129 , 130 , 131 , 132 , 133 , 137 , 138 , 140 , 141 , 142 In addition to the effect on cardiomyocyte survival, several miRNAs, namely miR-24, miR-98-5p, miR-125b, miR-126, miR-133a-3p, miR-150-5p, miR-338, miR-4732-3p, miR-31, miR-210, and miR-486-5p, loading into exosomes from cardiomyocytes, MSCs, or endothelial cells were identified to promote cardiac function recovery by promoting cardiomyocyte survival, anti-inflammation, angiogenesis, or anti-fibrosis. 114 , 117 , 118 , 120 , 124 , 127 , 131 , 138 , 141 , 142 Suggestively, exosomal miRNAs play momentous roles in coordinating responses to cardioprotective effects, i.e., by promoting cardiomyocyte survival and cardiac functional recovery. Notably, not all miRNAs encapsulated in exosome samples have a cardioprotective effect.…”

“…It has been uncovered that increasing the survival of cardiac endothelial cells, ameliorating cardiac angiogenesis, and mediating the recanalization of cardiac collaterals are great therapeutic targets. Secreted miRNAs encapsulated in exosomes derived from cardiomyocytes, MSCs, cardiac progenitor cells, dendritic cells, or patient serum, including miR-486-5p, 138 miR-494-3p, 139 miR-4732-3p, 141 miR-210, 109 miR-322, 135 miRNA-143, 110 miRNA-21-5p, 111 and miR-31, 117 could protect against myocardial ischemia via promoting cardiac angiogenesis and vascular regeneration, leading to accelerated blood flow to ischemic myocardium. Some miRNAs, such as miR-210, play a role via other effectors directly and indirectly.…”

Metabolically stressed adipocytes: mediators of cardioprotection via extracellular vesicle-mediated transport of oxidatively damaged mitochondria

“…However, the cardiac effect of adipose-derived sEVs is not always consistent. Multiple recent studies describe EV-mediated delivery of specific microRNA (miRNA) from adipose-derived stem cells that impact mouse models of cardiac ischemic injury ( 5 – 9 ). BAT-derived EVs blunt obesity-induced declines in cardiac function, but their delivered EVs were shown to accumulate mainly in the liver, spleen, and lungs, and the direct effects on the myocardium were not investigated ( 10 ).…”