Exosomes derived from miR‐129‐5p modified bone marrow mesenchymal stem cells represses ventricular remolding of mice with myocardial infarction

Abstract

Myocardial infraction (MI) is a severe disease with great mortality. Mesenchymal stem cells-derived exosomes display protection against MI. MicroRNA-129-5p was reported to exert anti-inflammation activity by targeting high mobility group box 1 (HMGB1). In the present study, the effects of MSCs derived exosomes overexpressing miR-129-5p on MI were evaluated. Bone marrow mesenchymal stem cells (BMSCs) were transfected with miR-129-5p for exosomes isolation. Myocardial infraction mice model was established and administrated exosomes overexpressing miR-129-5p. The cardiac function, expression of HMGB1, inflammatory cytokines, apoptosis and fibrosis in heart tissues were measured. miR-129-5p inhibited HMGB1 expression in BMSCs. Myocardial infraction mice treated with exosomes overexpressing miR-129-5p had enhanced cardiac function and decreased expression of HMGB1 and production of inflammatory cytokines. Exosomes overexpressing miR-129-5p further prevented apoptosis and fibrosis. Exosome-mediated transfer of miR-129-5p suppressed inflammation in MI mice by targeting HMGB1.

Myocardial fibrosis and calcification are attenuated by microRNA–129-5p targeting Asporin and Sox9 in cardiac fibroblasts

“…Recently miR–129-5p was shown to inhibit cardiomyocyte hypertrophy ( 18 , 19 , 29 , 30 ), and our FISH data show miR–129-5p expression in cardiomyocytes. Cardiomyocytes can affect CF differentiation via paracrine interactions ( 31 ); thus, we examined whether miR–129-5p expression in cardiomyocytes may affect CF-to-MF and CF-to OF transition.…”

“…Here, we show that the common mechanism behind CF-to-MF transition and CF-to-OF transition in nonischemic HF comprises the miR–129-5p/SOX9 and miR–129-5p/ASPN axes. Recently miR–129-5p was shown to inhibit cardiomyocyte hypertrophy ( 18 , 19 , 29 , 30 ). Although our study confirms the role of miR-129 in regulating cardiac hypertrophy as well, ours is the first study to our knowledge to investigate the role of miR–129-5p in regulating fibrosis and calcification in the heart by targeting CF and not cardiomyocytes.…”

Mesenchymal Stem Cell-Derived Exosomes for Myocardial Infarction Treatment

“…Direct injection of MSC-EXO with miR-183-5p overexpression has been shown to result in better cardiac function via suppression of apoptosis and oxidative stress of cardiomyocytes by targeting FOXO1 [124]. Administration of EXO derived from miR-129-5p-modified MSCs displayed enhanced cardiac function following MI in mice by downregulating apoptosis of cardiomyocytes and production of inflammatory cytokines via targeting of HMGB1 [125]. Moreover, EXO derived from miR-126-overexpressing adipose-MSCs demonstrated better beneficial effects by inhibiting cardiac fibrosis and inflammatory cytokine expression and increasing angiogenesis [80].…”

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.…”