Rho kinases in cardiovascular physiology and pathophysiology

The effect of fasudil

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Rho kinase (ROCK) is a major downstream effector of the small GTPase RhoA. ROCK family, consisting of ROCK1 and ROCK2, plays central roles in the organization of actin cytoskeleton and is involved in a wide range of fundamental cellular functions, such as contraction, adhesion, migration, proliferation, and apoptosis. Due to the discovery of effective inhibitors, such as fasudil and Y27632, the biological roles of ROCK have been extensively explored with particular attention on the cardiovascular system. In many preclinical models of cardiovascular diseases, including vasospasm, arteriosclerosis, hypertension, pulmonary hypertension, stroke, ischemia-reperfusion injury, and heart failure, ROCK inhibitors have shown a remarkable efficacy in reducing vascular smooth muscle cell hypercontraction, endothelial dysfunction, inflammatory cell recruitment, vascular remodeling, and cardiac remodeling. Moreover, fasudil has been used in the clinical trials of several cardiovascular diseases. The continuing utilization of available pharmacological inhibitors and the development of more potent or isoform-selective inhibitors in ROCK signaling research and in treating human diseases are escalating. In this review, we discuss the recent molecular, cellular, animal, and clinical studies with a focus on the current understanding of ROCK signaling in cardiovascular physiology and diseases. We particularly note that emerging evidence suggests that selective targeting ROCK isoform based on the disease pathophysiology may represent a novel therapeutic approach for the disease treatment including cardiovascular diseases.

Original languageEnglish
Pages (from-to)341-354
Number of pages14
JournalJournal of Cardiovascular Pharmacology
Volume62
Issue number4
DOIs
StatePublished - Oct 2013

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Cardiovascular Physiological Phenomena
rho-Associated Kinases
Cardiovascular Diseases
Protein Isoforms
Monomeric GTP-Binding Proteins
Arteriosclerosis
Cardiovascular System
Reperfusion Injury
Actin Cytoskeleton
Vascular Smooth Muscle
Pulmonary Hypertension
Smooth Muscle Myocytes
Heart Failure
Stroke
Clinical Trials
Pharmacology
Apoptosis
Hypertension
fasudil
Research

Keywords

  • cardiovascular disease
  • fasudil
  • inhibitor
  • Rho kinase

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Rho kinases in cardiovascular physiology and pathophysiology : The effect of fasudil. / Shi, Jianjian; Wei, Lei.

In: Journal of Cardiovascular Pharmacology, Vol. 62, No. 4, 10.2013, p. 341-354.

Research output: Contribution to journalArticle

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