Yang Huaxiang, Tan Mingjie, Gao Zhuqing, Wang Shanshan, Lyu Lingna, Ding Huiguo
Department of Gastroenterology and Hepatology, Beijing You'an Hospital Affiliated to Capital Medical University, Beijing, China.
Cell Biology Laboratory, Beijing Institute of Hepatology, Beijing, China.
J Clin Transl Hepatol. 2023 Jun 28;11(3):675-681. doi: 10.14218/JCTH.2022.00217. Epub 2023 Jan 4.
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 (HS) synthesis, and hypoxia-induced angiogenic responses. HS, a novel gas transmitter, plays an important role in various pathophysiological processes, especially in hepatic angiogenesis. Inhibition of endogenous HS 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. HS has also been shown to be involved in the regulation of VEGF-mediated angiogenesis. Therefore, HS and HIF-1 may be potential therapeutic targets for portal hypertension. The effects of HS donors or prodrugs on the hemodynamics of portal hypertension and the mechanism of HS-induced angiogenesis are promising areas for future research.
门静脉高压症的发病机制尚不清楚，据信涉及肝窦内皮细胞（LSEC）功能障碍、肝星状细胞（HSC）激活、内源性硫化氢（HS）合成失调以及缺氧诱导的血管生成反应。HS作为一种新型气体递质，在各种病理生理过程中发挥重要作用，尤其是在肝脏血管生成方面。通过药物或基因沉默抑制内源性HS合酶可能会增强内皮细胞的血管生成反应。缺氧诱导因子-1（HIF-1）是缺氧的主要转录因子，它通过上调HSC和LSEC中的血管内皮生长因子（VEGF）来诱导肝脏血管生成。HS也已被证明参与VEGF介导的血管生成调节。因此，HS和HIF-1可能是门静脉高压症的潜在治疗靶点。HS供体或前药对门静脉高压血流动力学的影响以及HS诱导血管生成的机制是未来研究的有前景的领域。
