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PMID: 16469861 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Physiological role of ROCKs in the cardiovascular system.

American journal of physiology. Cell physiology ·Vol. 290 ·No. 3 ·2006-03-00 ·Pages C661-8

Noma K, Oyama N, Liao JK

Abstract

Rho-associated kinases (ROCKs), the immediate downstream targets of RhoA, are ubiquitously expressed serine-threonine protein kinases that are involved in diverse cellular functions, including smooth muscle contraction, actin cytoskeleton organization, cell adhesion and motility, and gene expression. Recent studies have shown that ROCKs may play a pivotal role in cardiovascular diseases such as vasospastic angina, ischemic stroke, and heart failure. Indeed, inhibition of ROCKs by statins or other selective inhibitors leads to the upregulation and activation of endothelial nitric oxide synthase (eNOS) and reduction of vascular inflammation and atherosclerosis. Thus inhibition of ROCKs may contribute to some of the cholesterol-independent beneficial effects of statin therapy. Currently, two ROCK isoforms have been identified, ROCK1 and ROCK2. Because ROCK inhibitors are nonselective with respect to ROCK1 and ROCK2 and also, in some cases, may be nonspecific with respect to other ROCK-related kinases such as myristolated alanine-rich C kinase substrate (MARCKS), protein kinase A, and protein kinase C, the precise role of ROCKs in cardiovascular disease remains unknown. However, with the recent development of ROCK1- and ROCK2-knockout mice, further dissection of ROCK signaling pathways is now possible. Herein we review what is known about the physiological role of ROCKs in the cardiovascular system and speculate about how inhibition of ROCKs could provide cardiovascular benefits.

MeSH Terms
Animals Cardiovascular Diseases/enzymology,metabolism Cardiovascular System/enzymology,metabolism Gene Expression Regulation, Enzymologic Humans Intracellular Signaling Peptides and Proteins Protein Serine-Threonine Kinases/antagonists & inhibitors,chemistry,genetics,metabolism rho-Associated Kinases
Chemicals
Intracellular Signaling Peptides and Proteins Protein Serine-Threonine Kinases ROCK1 protein, human ROCK2 protein, human rho-Associated Kinases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Noma Kensuke
Brigham and Women's Hospital, 65 Landsdowne St., Rm. 275, Cambridge, MA, USA.
Oyama Naotsugu
Liao James K
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Article Info
Journal
American journal of physiology. Cell physiology
Abbr.
Am J Physiol Cell Physiol
ISSN
0363-6143
DOI
10.1152/ajpcell.00459.2005
Published
2006-03-00
Pages
C661-8
Language
English
Region
United States
NLM ID
100901225
PMCID
PMC2692274
Subset
IM
Grants
NINDS NIH HHS · P01 NS010828 · United States
NHLBI NIH HHS · R01 HL080187-01A1 · United States
NIDDK NIH HHS · R01 DK062729-01A1 · United States
NHLBI NIH HHS · R01 HL070274-02 · United States
NINDS NIH HHS · P01 NS010828-330036 · United States
NHLBI NIH HHS · R01 HL052233-08 · United States
NINDS NIH HHS · P50 NS010828-300036 · United States
NIDDK NIH HHS · R01 DK062729-02 · United States
NHLBI NIH HHS · R01 HL070274-01 · United States
NHLBI NIH HHS · R01 HL052233-09 · United States
NINDS NIH HHS · NS-10828 · United States
NINDS NIH HHS · P50 NS010828 · United States
NINDS NIH HHS · F32 NS010828 · United States
NIDDK NIH HHS · R01 DK062729-03 · United States
NHLBI NIH HHS · R01 HL052233 · United States
NIDDK NIH HHS · R01 DK062729 · United States
NHLBI NIH HHS · R01 HL070274 · United States
NHLBI NIH HHS · R01 HL070274-03 · United States
NINDS NIH HHS · P50 NS010828-290036 · United States
NHLBI NIH HHS · R01 HL080187 · United States
NIDDK NIH HHS · R01 DK062729-04 · United States
NHLBI NIH HHS · HL-52233 · United States
External Links
PubMed source DOI: 10.1152/ajpcell.00459.2005 PMC Full Text View journal details
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