Development of Rho-kinase inhibitors for cardiovascular medicine

Hiroaki Shimokawa, Mamunur Rashid

Research output: Contribution to journalReview articlepeer-review

202 Citations (Scopus)

Abstract

Rho-kinase (ROCK) is one of the downstream effectors of the small G-protein Rho. The Rho-ROCK pathway has an important role in mediating various cellular functions, including contraction, actin cytoskeleton organization, cell adhesion and motility, proliferation, cytokinesis and gene expression, all of which are involved in the pathogenesis of cardiovascular disease. Indeed, vascular smooth muscle cells, endothelial cells, adventitial cells, cardiomyocytes and nerve cells all undergo pathophysiological changes through the ROCK pathway. Abnormal activation of this pathway is associated with the pathogenesis of various cardiovascular diseases such as hypertension, coronary and cerebral vasospasm, restenosis, atherosclerosis, stroke and heart failure, although the roles of the ROCK isoforms (ROCK1 and ROCK2) remain to be elucidated. In this article, we review the information about the therapeutic importance of the ROCK pathway and summarize the current status of the development of ROCK inhibitors.

Original languageEnglish
Pages (from-to)296-302
Number of pages7
JournalTrends in Pharmacological Sciences
Volume28
Issue number6
DOIs
Publication statusPublished - 2007 Jun

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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