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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hypertens. Feb 23, 2016; 6(1): 18-35
Published online Feb 23, 2016. doi: 10.5494/wjh.v6.i1.18
RhoA signaling and blood pressure: The consequence of failing to “Tone it Down”
Xue Bai, Rachel Dee, Kevin D Mangum, Christopher P Mack, Joan M Taylor
Xue Bai, Rachel Dee, Kevin D Mangum, Christopher P Mack, Joan M Taylor, Department of Pathology and Laboratory Medicine, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States
Author contributions: Bai X, Dee R and Mangum KD contributed equally to this work; all authors contributed to literature review and analysis, drafting and critical revision and editing, and approval of the final version.
Supported by the National Heart, Lung, and Blood Institute, National Institutes of Health to Taylor JM, Nos. HL-081844 and HL-071054; and the Muscular Dystrophy Association to Taylor JM, No. MDA255577.
Conflict-of-interest statement: No conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Joan M Taylor, PhD, Department of Pathology and Laboratory Medicine, McAllister Heart Institute, University of North Carolina at Chapel Hill, CB7525, 501 Brinkhous-Bullitt Bld, Chapel Hill, NC 27599, United States. jmt3x@med.unc.edu
Telephone: +1-919-8435511 Fax: +1-919-9666718
Received: September 30, 2015
Peer-review started: October 8, 2015
First decision: November 6, 2015
Revised: November 24, 2015
Accepted: January 21, 2016
Article in press: January 22, 2016
Published online: February 23, 2016
Processing time: 146 Days and 10.1 Hours
Abstract

Uncontrolled high blood pressure is a major risk factor for heart attack, stroke, and kidney failure and contributes to an estimated 25% of deaths worldwide. Despite numerous treatment options, estimates project that reasonable blood pressure (BP) control is achieved in only about half of hypertensive patients. Improvements in the detection and management of hypertension will undoubtedly be accomplished through a better understanding of the complex etiology of this disease and a more comprehensive inventory of the genes and genetic variants that influence BP regulation. Recent studies (primarily in pre-clinical models) indicate that the small GTPase RhoA and its downstream target, Rho kinase, play an important role in regulating BP homeostasis. Herein, we summarize the underlying mechanisms and highlight signaling pathways and regulators that impart tight spatial-temporal control of RhoA activity. We also discuss known allelic variations in the RhoA pathway and consider how these polymorphisms may affect genetic risk for hypertension and its clinical manifestations. Finally, we summarize the current (albeit limited) clinical data on the efficacy of targeting the RhoA pathway in hypertensive patients.

Keywords: Hypertension; Blood pressure; RhoA; Smooth muscle contraction; Guanine nucleotide exchange factor; GTPase activating protein; Polymorphisms

Core tip: Studies (primarily in pre-clinical models) indicate that the small GTPase RhoA and its downstream target, Rho kinase, play an important role in regulating blood pressure homeostasis. Herein, we summarize the underlying mechanisms and highlight signaling pathways and regulators that impart tight spatial-temporal control of RhoA activity. We also discuss known allelic variations in the RhoA pathway and consider how these polymorphisms may affect genetic risk for hypertension and its clinical manifestations. Finally, we summarize the current (albeit limited) clinical data on the efficacy of targeting the RhoA pathway in hypertensive patients.