RhoA/Rho-Kinase in the Cardiovascular System
Top Cited Papers
- 22 January 2016
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation Research
- Vol. 118 (2), 352-366
- https://doi.org/10.1161/circresaha.115.306532
Abstract
Twenty years ago, Rho-kinase was identified as an important downstream effector of the small GTP-binding protein, RhoA. Thereafter, a series of studies demonstrated the important roles of Rho-kinase in the cardiovascular system. The RhoA/Rho-kinase pathway is now widely known to play important roles in many cellular functions, including contraction, motility, proliferation, and apoptosis, and its excessive activity induces oxidative stress and promotes the development of cardiovascular diseases. Furthermore, the important role of Rho-kinase has been demonstrated in the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, and heart failure. Cyclophilin A is secreted by vascular smooth muscle cells and inflammatory cells and activated platelets in a Rho-kinase–dependent manner, playing important roles in a wide range of cardiovascular diseases. Thus, the RhoA/Rho-kinase pathway plays crucial roles under both physiological and pathological conditions and is an important therapeutic target in cardiovascular medicine. Recently, functional differences between ROCK1 and ROCK2 have been reported in vitro. ROCK1 is specifically cleaved by caspase-3, whereas granzyme B cleaves ROCK2. However, limited information is available on the functional differences and interactions between ROCK1 and ROCK2 in the cardiovascular system in vivo. Herein, we will review the recent advances about the importance of RhoA/Rho-kinase in the cardiovascular system.Keywords
This publication has 95 references indexed in Scilit:
- Single atom substitution in mouse protein kinase G eliminates oxidant sensing to cause hypertensionNature Medicine, 2012
- Redox modification of cell signaling in the cardiovascular systemJournal of Molecular and Cellular Cardiology, 2011
- Caspase-activated ROCK-1 allows erythroblast terminal maturation independently of cytokine-induced Rho signalingCell Death & Differentiation, 2010
- Cyclophilin A enhances vascular oxidative stress and the development of angiotensin II–induced aortic aneurysmsNature Medicine, 2009
- Mechanism of multi-site phosphorylation from a ROCK-I:RhoE complex structureThe EMBO Journal, 2008
- The Functional Role of the Renin–Angiotensin System in Pregnancy and PreeclampsiaPlacenta, 2008
- Mechanisms of Disease: molecular genetics of arrhythmogenic right ventricular dysplasia/cardiomyopathyNature Clinical Practice Cardiovascular Medicine, 2008
- Cyclophilin A produced by thymocytes regulates the migration of murine bone marrow cellsCellular Immunology, 2007
- New Roles of Myosin II during Vesicle Transport and Fusion in Chromaffin CellsPublished by Elsevier BV ,2004
- Inflammation in atherosclerosisNature, 2002