Yang Guangdong, Wang Rui
Cardiovascular and Metabolic Research Unit, Lakehead University, Thunder Bay, ON, Canada.
Handb Exp Pharmacol. 2015;230:85-110. doi: 10.1007/978-3-319-18144-8_4.
The physiological and biomedical importance of hydrogen sulfide (H2S) has been fully recognized in the cardiovascular system as well as in the rest of the body. In blood vessels, cystathionine γ-lyase (CSE) is a major H2S-producing enzyme expressed in both smooth muscle and endothelium as well as periadventitial adipose tissues. Regulation of H2S production from CSE is controlled by a complex integration of transcriptional, posttranscriptional, and posttranslational mechanisms in blood vessels. In smooth muscle cells, H2S regulates cell apoptosis, phenotypic switch, relaxation and contraction, and calcification. In endothelial cells, H2S controls cell proliferation, cellular senescence, oxidative stress, inflammation, etc. H2S interacts with nitric oxide and acts as an endothelium-derived relaxing factor and an endothelium-derived hyperpolarizing factor. H2S generated from periadventitial adipose tissues acts as an adipocyte-derived relaxing factor and modulates the vascular tone. Extensive evidence has demonstrated the beneficial roles of the CSE/H2S system in various blood vessel diseases, such as hypertension, atherosclerosis, and aortic aneurysm. The important roles signaling in the cardiovascular system merit further intensive and extensive investigation. H2S-releasing agents and CSE activators will find their great applications in the prevention and treatment of blood vessel-related disorders.
硫化氢(H₂S)在心血管系统以及身体其他部位的生理和生物医学重要性已得到充分认可。在血管中,胱硫醚γ-裂解酶(CSE)是一种主要的H₂S生成酶,在平滑肌、内皮以及血管外膜脂肪组织中均有表达。血管中CSE产生H₂S的过程受到转录、转录后和翻译后机制的复杂整合调控。在平滑肌细胞中,H₂S调节细胞凋亡、表型转换、舒张和收缩以及钙化。在内皮细胞中,H₂S控制细胞增殖、细胞衰老、氧化应激、炎症等。H₂S与一氧化氮相互作用,充当内皮源性舒张因子和内皮源性超极化因子。血管外膜脂肪组织产生的H₂S充当脂肪细胞源性舒张因子并调节血管张力。大量证据表明CSE/H₂S系统在各种血管疾病(如高血压、动脉粥样硬化和主动脉瘤)中具有有益作用。该信号通路在心血管系统中的重要作用值得进一步深入广泛研究。H₂S释放剂和CSE激活剂将在血管相关疾病的预防和治疗中找到其巨大应用价值。