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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Tumor suppressor ras-association domain family 1 Isoform A Is a novel regulator of cardiac hypertrophy
Circulation, Volume 120, No. 7, Year 2009
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Description
Background: Ras signaling regulates a number of important processes in the heart, including cell growth and hypertrophy. Although it is known that defective Ras signaling is associated with Noonan, Costello, and other syndromes that are characterized by tumor formation and cardiac hypertrophy, little is known about factors that may control it. Here we investigate the role of Ras effector Ras-association domain family 1 isoform A (RASSF1A) in regulating myocardial hypertrophy. METHODS AND RESULTS-: A significant downregulation of RASSF1A expression was observed in hypertrophic mouse hearts, as well as in failing human hearts. To further investigate the role of RASSF1A in cardiac (patho)physiology, we used RASSF1A knock-out (RASSF1A) mice and neonatal rat cardiomyocytes with adenoviral overexpression of RASSF1A. Ablation of RASSF1A in mice significantly enhanced the hypertrophic response to transverse aortic constriction (64.2% increase in heart weight/body weight ratio in RASSF1A mice compared with 32.4% in wild type). Consistent with the in vivo data, overexpression of RASSF1A in cardiomyocytes markedly reduced the cellular hypertrophic response to phenylephrine stimulation. Analysis of molecular signaling events in isolated cardiomyocytes indicated that RASSF1A inhibited extracellular regulated kinase 1/2 activation, likely by blocking the binding of Raf1 to active Ras. CONCLUSIONS-: Our data establish RASSF1A as a novel inhibitor of cardiac hypertrophy by modulating the extracellular regulated kinase 1/2 pathway. © 2009 American Heart Association, Inc.
Authors & Co-Authors
Oceandy, Delvac
United Kingdom, Manchester
The University of Manchester
Pickard, Adam
United Kingdom, Manchester
The University of Manchester
Prehar, Sukhpal
United Kingdom, Manchester
The University of Manchester
Zi, Min
United Kingdom, Manchester
The University of Manchester
Mohamed, Tamer M.A.
United Kingdom, Manchester
The University of Manchester
Egypt, Zagazig
Faculty of Pharmacy
Stanley, Peter J.
United Kingdom, Manchester
The University of Manchester
Baudoin, Florence M.H.
United Kingdom, Manchester
The University of Manchester
Nadif, Raja
United Kingdom, Manchester
The University of Manchester
Tommasi, Stella
United States, Duarte
City of Hope National Med Center
Pfeifer, Gerd P.
United States, Duarte
City of Hope National Med Center
Armesilla, Angel L.
United Kingdom, Wolverhampton
University of Wolverhampton
Elizabeth J. Cartwright, Elizabeth J.
United Kingdom, Manchester
The University of Manchester
Neyses, Ludwig
United Kingdom, Manchester
The University of Manchester
Statistics
Citations: 69
Authors: 13
Affiliations: 4
Identifiers
Doi:
10.1161/CIRCULATIONAHA.109.868554
ISSN:
00097322
e-ISSN:
15244539
Research Areas
Cancer
Maternal And Child Health
Noncommunicable Diseases