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.