Shimokawa Hiroaki, Satoh Kimio
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
J Cardiovasc Pharmacol. 2015 May;65(5):412-8. doi: 10.1097/FJC.0000000000000159.
Vascular-derived hydrogen peroxide (H2O2) serves as an important signaling molecule in the cardiovascular system and contributes to vascular homeostasis. H2O2 is a second messenger, transducing the oxidative signal into biological responses through posttranslational protein modification. The balance between oxidant and antioxidant systems regulates intracellular redox status, and their imbalance causes oxidative or reductive stress, leading to cellular damage in cardiovascular systems. Excessive H2O2 deteriorates vascular functions and promotes vascular disease through multiple pathways. The RhoA/Rho-kinase pathway plays an important role in various fundamental cellular functions, including production of excessive reactive oxygen species, leading to the development of cardiovascular diseases. Rho-kinase (ROCK1 and ROCK2) belongs to the family of serine/threonine kinases and is an important downstream effector of the small GTP-binding protein RhoA. Rho-kinase plays a crucial role in the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, stroke, and heart failure. Thus, Rho-kinase inhibitors may be useful for the treatment of cardiovascular diseases in humans. In this review, we will briefly discuss the roles of vascular-derived H2O2 and review the recent progress in the translational research on the therapeutic importance of the Rho-kinase pathway in cardiovascular medicine.
血管源性过氧化氢(H2O2)是心血管系统中一种重要的信号分子,有助于维持血管稳态。H2O2作为第二信使,通过翻译后蛋白质修饰将氧化信号转化为生物学反应。氧化系统与抗氧化系统之间的平衡调节细胞内氧化还原状态,二者失衡会导致氧化应激或还原应激,进而造成心血管系统细胞损伤。过量的H2O2会通过多种途径损害血管功能并促进血管疾病的发生。RhoA/Rho激酶途径在多种基本细胞功能中发挥重要作用,包括产生过量的活性氧,从而导致心血管疾病的发展。Rho激酶(ROCK1和ROCK2)属于丝氨酸/苏氨酸激酶家族,是小GTP结合蛋白RhoA的重要下游效应器。Rho激酶在血管痉挛、动脉硬化、缺血/再灌注损伤、高血压、肺动脉高压、中风和心力衰竭的发病机制中起关键作用。因此,Rho激酶抑制剂可能对人类心血管疾病的治疗有用。在这篇综述中,我们将简要讨论血管源性H2O2的作用,并回顾Rho激酶途径在心血管医学治疗重要性方面的转化研究最新进展。