Gaseous bioactive molecules including nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S), are able to regulate key functions in vascular endothelial cells (ECs). In particular, H2S acts as a vasorelaxant and antiinflammatory agent as well as a stimulator of angiogenesis. Here we investigate the roles of H2S in different vascular cell models, including a pathological one. We focused on the effects of this molecule on calcium channels, and the following intracellular calcium (Cai) signaling. Normal ECs (HMECs) and tumor-derived ECs (BTECs) respond to NaHS administration with Cai increase entirely due to Ca2+ entry from the extracellular medium. Interestingly, BTECs are more sensitive than HMECs, being responsive to lower concentrations of H2S donor NaHS (below 1μM). Moreover NaHS enhances BTEC, but not HMEC, migration. Inhibition of endogenous H2S by PAG (a CSE inhibitor) decreases the percentage of VEGF-responding cells in Ca2+ imaging experiments, and reduces BTECs migration. NaHS induces dose-dependent reversible Cai increases also in rat cardiac microvascular ECs (CMECs). Similarly to what observed in HMECs and BTECs, the response is prevented by removing either extracellular Na+ or Ca2+ and therefore dependent on calcium entry. Finally, we show the ability of H2S donors to trigger Cai waves in human circulating endothelial progenitor cells (EPCs). The dose-response curve is different from that observed in CMECs. In conclusion, H2S activates calcium channels is different types of mature ECs as well as in EC precursors, with different sensitivities and functional effects.
SPECIFICITY OF CALCIUM SIGNALING INDUCED BY HYDROGEN SULFIDE IN DIFFERENT ENDOTHELIAL CELL TYPES
AVANZATO, DANIELE;MANCARDI, Daniele;MUNARON, Luca Maria
2012-01-01
Abstract
Gaseous bioactive molecules including nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S), are able to regulate key functions in vascular endothelial cells (ECs). In particular, H2S acts as a vasorelaxant and antiinflammatory agent as well as a stimulator of angiogenesis. Here we investigate the roles of H2S in different vascular cell models, including a pathological one. We focused on the effects of this molecule on calcium channels, and the following intracellular calcium (Cai) signaling. Normal ECs (HMECs) and tumor-derived ECs (BTECs) respond to NaHS administration with Cai increase entirely due to Ca2+ entry from the extracellular medium. Interestingly, BTECs are more sensitive than HMECs, being responsive to lower concentrations of H2S donor NaHS (below 1μM). Moreover NaHS enhances BTEC, but not HMEC, migration. Inhibition of endogenous H2S by PAG (a CSE inhibitor) decreases the percentage of VEGF-responding cells in Ca2+ imaging experiments, and reduces BTECs migration. NaHS induces dose-dependent reversible Cai increases also in rat cardiac microvascular ECs (CMECs). Similarly to what observed in HMECs and BTECs, the response is prevented by removing either extracellular Na+ or Ca2+ and therefore dependent on calcium entry. Finally, we show the ability of H2S donors to trigger Cai waves in human circulating endothelial progenitor cells (EPCs). The dose-response curve is different from that observed in CMECs. In conclusion, H2S activates calcium channels is different types of mature ECs as well as in EC precursors, with different sensitivities and functional effects.
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