The pathogenesis of portal hypertension remains unclear,and is believed to involve dysfunction of liver sinusoidal endotheli-al cells(LSEC),activation of hepatic stellate cells(HSC),dys-regulation of endogenous hydrog...The pathogenesis of portal hypertension remains unclear,and is believed to involve dysfunction of liver sinusoidal endotheli-al cells(LSEC),activation of hepatic stellate cells(HSC),dys-regulation of endogenous hydrogen sulfide(H_(2)S)synthesis,and hypoxia-induced angiogenic responses.H_(2)S,a novel gas transmitter,plays an important role in various pathophysi-ological processes,especially in hepatic angiogenesis.Inhibi-tion of endogenous H_(2)S synthase by pharmaceutical agents or gene silencing may enhance the angiogenic response of en-dothelial cells.Hypoxia-inducible factor-1(HIF-1)is the main transcription factor of hypoxia,which induces hepatic angio-genesis through up-regulation of vascular endothelial growth factor(VEGF)in HSC and LSEC.H_(2)S has also been shown to be involved in the regulation of VEGF-mediated angiogen-esis.Therefore,H_(2)S and HIF-1 may be potential therapeutic targets for portal hypertension.The effects of H_(2)S donors or prodrugs on the hemodynamics of portal hypertension and the mechanism of H_(2)S-induced angiogenesis are promising areas for future research.展开更多
基金the National Natural Science Foundation(81970525)Sino-German Coopera-tion Group(GZ1517).
文摘The pathogenesis of portal hypertension remains unclear,and is believed to involve dysfunction of liver sinusoidal endotheli-al cells(LSEC),activation of hepatic stellate cells(HSC),dys-regulation of endogenous hydrogen sulfide(H_(2)S)synthesis,and hypoxia-induced angiogenic responses.H_(2)S,a novel gas transmitter,plays an important role in various pathophysi-ological processes,especially in hepatic angiogenesis.Inhibi-tion of endogenous H_(2)S synthase by pharmaceutical agents or gene silencing may enhance the angiogenic response of en-dothelial cells.Hypoxia-inducible factor-1(HIF-1)is the main transcription factor of hypoxia,which induces hepatic angio-genesis through up-regulation of vascular endothelial growth factor(VEGF)in HSC and LSEC.H_(2)S has also been shown to be involved in the regulation of VEGF-mediated angiogen-esis.Therefore,H_(2)S and HIF-1 may be potential therapeutic targets for portal hypertension.The effects of H_(2)S donors or prodrugs on the hemodynamics of portal hypertension and the mechanism of H_(2)S-induced angiogenesis are promising areas for future research.
