Prosurvival communication between endothelial cells and mesenchymal stem cells through exosomes containing HIF1-alpha

The transcription factor hypoxia-inducible factor 1 alpha (HIF1-a) is a downstream regulator of hypoxia response and neovascularization in adult myocardium. As exosomes mediate cell-cell communication in many stress responses, we investigated the release of exosomes containing HIF1-a (HIF1a-exo) by arterial endothelial cells (pAOECs) and mesenchymal stem cells (pMSCs), which characterize the myocardial angiogenesis. We also evaluated the transport of HIF1a-exo between the two cell lines under normoxia and hypoxia. Up to 72h of normoxic monocolture, the release of HIF1a-exo by pAOECs did not change compared to baseline, yet HIF1-a expression increased by 80±5% (p<0.001); although, HIF1-a espression and HIF1a-exo secretion by pMSCs were lower than pAOECs, but higher at 72h than baseline (p<0.05). At 72h of normoxic co-culture, the level of HIF1α-exo wa s similar to single-pAOECs culture and increased by 175±11% compared to baseline (P<0.001), even if HIF1-α level in pAOECs was reduced by 40±7% than pMSCs (p<0.05). The number of both cell lines was significantly higher in co-culture compared to each monocolture. At 72h of hypoxic co-colture, the number of pAOECs and pMSCs was respectively reduced by 44±5% (p<0.001) and 32±2% (p<0.001). Even if HIF1-a expression was higher in co-cultered pMSCs, the release of HIF1a-exo was lower than hypoxic monoculture and similar to normoxia. In conclusion, the cross talk between pAOECs and pMSCs through HIF1a-exo is attenuated under hypoxia.