Kanagy Nancy L, Szabo Csaba, Papapetropoulos Andreas
Vascular Physiology Group, Department of Cell Biology and Physiology, School of Medicine, University of New Mexico, Albuquerque, New Mexico.
Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas.
Am J Physiol Cell Physiol. 2017 May 1;312(5):C537-C549. doi: 10.1152/ajpcell.00329.2016. Epub 2017 Feb 1.
Hydrogen sulfide (HS) is a ubiquitous signaling molecule with important functions in many mammalian organs and systems. Observations in the 1990s ascribed physiological actions to HS in the nervous system, proposing that this gasotransmitter acts as a neuromodulator. Soon after that, the vasodilating properties of HS were demonstrated. In the past decade, HS was shown to exert a multitude of physiological effects in the vessel wall. HS is produced by vascular cells and exhibits antioxidant, antiapoptotic, anti-inflammatory, and vasoactive properties. In this concise review, we have focused on the impact of HS on vascular structure and function with an emphasis on angiogenesis, vascular tone, vascular permeability and atherosclerosis. HS reduces arterial blood pressure, limits atheromatous plaque formation, and promotes vascularization of ischemic tissues. Although the beneficial properties of HS are well established, mechanistic insights into the molecular pathways implicated in disease prevention and treatment remain largely unexplored. Unraveling the targets and downstream effectors of HS in the vessel wall in the context of disease will aid in translation of preclinical observations. In addition, acute regulation of HS production is still poorly understood and additional work delineating the pathways regulating the enzymes that produce HS will allow pharmacological manipulation of this pathway. As the field continues to grow, we expect that HS-related compounds will find their way into clinical trials for diseases affecting the blood vessels.
硫化氢(HS)是一种普遍存在的信号分子,在许多哺乳动物器官和系统中具有重要功能。20世纪90年代的观察结果将HS在神经系统中的生理作用归因于此,提出这种气体递质作为一种神经调节剂发挥作用。此后不久,HS的血管舒张特性得到证实。在过去十年中,HS被证明在血管壁中发挥多种生理作用。HS由血管细胞产生,具有抗氧化、抗凋亡、抗炎和血管活性特性。在这篇简短的综述中,我们重点关注了HS对血管结构和功能的影响,重点是血管生成、血管张力、血管通透性和动脉粥样硬化。HS可降低动脉血压,限制动脉粥样斑块形成,并促进缺血组织的血管化。尽管HS的有益特性已得到充分证实,但对其在疾病预防和治疗中所涉及的分子途径的机制性见解仍 largely unexplored。在疾病背景下阐明HS在血管壁中的靶点和下游效应器将有助于临床前观察结果的转化。此外,对HS产生的急性调节仍知之甚少,进一步研究描绘调节产生HS的酶的途径将允许对该途径进行药理学操纵。随着该领域的不断发展,我们预计与HS相关的化合物将进入影响血管疾病的临床试验。