Rho kinase as a therapeutic target in cardiovascular disease

Michelle Surma, Lei Wei, Jianjian Shi

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Rho kinase (ROCK) belongs to the AGC (PKA/PKG/PKC) family of serine/threonine kinases and is a major downstream effector of the small GTPase RhoA. ROCK plays central roles in the organization of the actin cytoskeleton and is involved in a wide range of fundamental cellular functions such as contraction, adhesion, migration, proliferation and gene expression. Two ROCK isoforms, ROCK1 and ROCK2, are assumed to be functionally redundant, based largely on the major common activators, the high degree of homology within the kinase domain and studies from overexpression with kinase constructs and chemical inhibitors (e.g., Y27632 and fasudil), which inhibit both ROCK1 and ROCK2. Extensive experimental and clinical studies support a critical role for the RhoA/ROCK pathway in the vascular bed in the pathogenesis of cardiovascular diseases, in which increased ROCK activity mediates vascular smooth muscle cell hypercontraction, endothelial dysfunction, inflammatory cell recruitment and vascular remodeling. Recent experimental studies, using ROCK inhibitors or genetic mouse models, indicate that the RhoA/ROCK pathway in myocardium contributes to cardiac remodeling induced by ischemic injury or persistent hypertrophic stress, thereby leading to cardiac decompensation and heart failure. This article, based on recent molecular, cellular and animal studies, focuses on the current understanding of ROCK signaling in cardiovascular diseases and in the pathogenesis of heart failure.

Original languageEnglish
Pages (from-to)657-671
Number of pages15
JournalFuture Cardiology
Volume7
Issue number5
DOIs
StatePublished - Sep 2011

Fingerprint

rho-Associated Kinases
Cardiovascular Diseases
Heart Failure
Phosphotransferases
Monomeric GTP-Binding Proteins
Genetic Models
Actin Cytoskeleton
Vascular Smooth Muscle
Protein Kinase C
Smooth Muscle Myocytes
Blood Vessels
Myocardium
Protein Isoforms
Therapeutics
Gene Expression
Wounds and Injuries

Keywords

  • cardiovascular
  • disease
  • heart
  • inhibitor
  • Rho kinase
  • ROCK

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Molecular Medicine

Cite this

Rho kinase as a therapeutic target in cardiovascular disease. / Surma, Michelle; Wei, Lei; Shi, Jianjian.

In: Future Cardiology, Vol. 7, No. 5, 09.2011, p. 657-671.

Research output: Contribution to journalArticle

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