Abstract
The pathogenesis of portal hypertension remains unclear, and is believed to involve dysfunction of liver sinusoidal endothelial cells (LSEC), activation of hepatic stellate cells (HSC), dysregulation 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 pathophysiological processes, especially in hepatic angiogenesis. Inhibition of endogenous H(2)S synthase by pharmaceutical agents or gene silencing may enhance the angiogenic response of endothelial cells. Hypoxia-inducible factor-1 (HIF-1) is the main transcription factor of hypoxia, which induces hepatic angiogenesis 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 angiogenesis. 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.