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Journal of Cardiovascular Translational Research
Published in: Journal of Cardiovascular Translational Research 4/2010

Open Access 01-08-2010

Revisited and Revised: Is RhoA Always a Villain in Cardiac Pathophysiology?

Authors: Shigeki Miyamoto, Dominic P. Del Re, Sunny Y. Xiang, Xia Zhao, Geir Florholmen, Joan Heller Brown

Published in: Journal of Cardiovascular Translational Research | Issue 4/2010

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Abstract

The neonatal rat ventricular myocyte model of hypertrophy has provided tremendous insight with regard to signaling pathways regulating cardiac growth and gene expression. Many mediators thus discovered have been successfully extrapolated to the in vivo setting, as assessed using genetically engineered mice and physiological interventions. Studies in neonatal rat ventricular myocytes demonstrated a role for the small G-protein RhoA and its downstream effector kinase, Rho-associated coiled-coil containing protein kinase (ROCK), in agonist-mediated hypertrophy. Transgenic expression of RhoA in the heart does not phenocopy this response, however, nor does genetic deletion of ROCK prevent hypertrophy. Pharmacologic inhibition of ROCK has effects most consistent with roles for RhoA signaling in the development of heart failure or responses to ischemic damage. Whether signals elicited downstream of RhoA promote cell death or survival and are deleterious or salutary is, however, context and cell-type dependent. The concepts discussed above are reviewed, and the hypothesis that RhoA might protect cardiomyocytes from ischemia and other insults is presented. Novel RhoA targets including phospholipid regulated and regulating enzymes (Akt, PI kinases, phospholipase C, protein kinases C and D) and serum response element-mediated transcriptional responses are considered as possible pathways through which RhoA could affect cardiomyocyte survival.
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Metadata
Title
Revisited and Revised: Is RhoA Always a Villain in Cardiac Pathophysiology?
Authors
Shigeki Miyamoto
Dominic P. Del Re
Sunny Y. Xiang
Xia Zhao
Geir Florholmen
Joan Heller Brown
Publication date
01-08-2010
Publisher
Springer US
Published in
Journal of Cardiovascular Translational Research / Issue 4/2010
Print ISSN: 1937-5387
Electronic ISSN: 1937-5395
DOI
https://doi.org/10.1007/s12265-010-9192-8

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