Emergence of hydrogen sulfide as an endogenous gaseous signaling molecule in cardiovascular disease.
Emergence of hydrogen sulfide as an endogenous gaseous signaling molecule in cardiovascular disease.
复制标题
DOI：
10.1161/circresaha.114.300505
复制
发表时间：
2014-02-14
影响因子：
20.1
通讯作者：
Lefer DJ
中科院分区：
文献类型：
--
作者：
Polhemus DJ;Lefer DJ
长期以来，硫化氢 (H2S) 被认为是一种恶臭且剧毒的气体，最近的实验研究表明，包括人类在内的所有哺乳动物物种都会通过酶促产生硫化氢 (H2S)，并发挥许多关键作用来促进心血管稳态和健康。在过去的15年里，科学家们已经确定H2S是由三种内源性酶产生的，并对内皮细胞、平滑肌细胞、炎症细胞、线粒体、内质网和核转录因子产生强大的影响。这些效应已在多个器官系统中得到报道，并且绝大多数数据清楚地表明内源酶产生的 H2S 发挥细胞保护作用。最近调查心血管疾病的临床前研究表明，施用生理或药理学水平的 H2S 可以减轻心肌损伤、保护血管、限制炎症和调节血压。 H2S 已成为类似于一氧化氮 (NO) 和一氧化碳 (CO) 的关键心血管信号分子，对心脏和循环产生深远影响（图 1）。我们对 H2S 如何引发保护作用的了解不断加深，加上新型 H2S 释放剂的快速开发，导致人们对这种短暂气体分子的临床转化热情高涨。本综述将探讨我们目前对 H2S 在心血管系统中的作用的了解，重点是 H2S、NO 和 CO 之间的治疗潜力和分子串扰。
Long recognized as a malodorous and highly toxic gas, recent experimental studies have revealed that hydrogen sulfide (H2S) is produced enzymatically in all mammalian species including man and exerts a number of critical actions to promote cardiovascular homeostasis and health. During the past 15 years, scientists have determined that H2S is produced by three endogenous enzymes and exerts powerful effects on endothelial cells, smooth muscle cells, inflammatory cells, mitochondria, endoplasmic reticulum, and nuclear transcription factors. These effects have been reported in multiple organ systems and the vast majority of data clearly indicate that H2S produced by the endogenous enzymes exerts cytoprotective actions. Recent preclinical studies investigating cardiovascular diseases have demonstrated that the administration of physiological or pharmacological levels of H2S attenuates myocardial injury, protects blood vessels, limits inflammation, and regulates blood pressure. H2S has emerged as a critical cardiovascular signaling molecule similar to nitric oxide (NO) and carbon monoxide (CO) with a profound impact on the heart and circulation (Figure 1). Our improved understanding of how H2S elicits protective actions, coupled with the very rapid development of novel H2S releasing agents, has resulted in heightened enthusiasm for the clinical translation of this ephemeral gaseous molecule. This review will examine our current state of knowledge regarding the actions of H2S within the cardiovascular system with an emphasis on the therapeutic potential and molecular crosstalk between H2S, NO, and CO.