HIF-1α overexpression in adipose mesenchymal stem cell-derived exosomes ameliorate hypoxia-induced dysfunction and inflammation in HUVECs

Abstract Background Increasing evidence suggests that ADSCs execute their paracrine function via the secretion of exosomes, especially under hypoxic conditions. However, the mechanisms by which ADSCs-derived exosomes (ADSC-exos) enhance angiogenesis under hypoxia remain unclear. Methods Exosomes were isolated from HIF-1α-modified ADSCs culture supernatants. To investigate the effects HIF-1α-ADSC-exos on HUVECs, cell growth, apoptosis, and tube formation assay were performed with or without HIF-1α-ADSC-exos. Moreover, to determine the function of HIF-1α-ADSC-exos, the therapeutic effects of ADSC-exos and HIF-1α-ADSC-exos were examined in PAH rats. Results Exosomes released by HIF-1α-modified ADSCs rescued the impaired angiogenic ability, migratory function, and inflammatory factors of hypoxia-injured HUVECs, with increased SDF-1α, Rac1, Rac2, VEGF and IL-10 expression. Furthermore, exos-HIF-1α activated SIRT3 to enhance angiogenesis in HUVECs and induced IL-10 expression to inhibit inflammatory response. Block SIRT3 or SDF-1α abolished the angiogenic effect in HUVECs. Conclusion Our findings indicated that the SIRT3 contributed a crucial role in HIF-1α-ADSC-exos in tissue repair under hypoxia.