Regulator of G protein signaling 5 protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload
Open Access
- 19 July 2010
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 107 (31), 13818-13823
- https://doi.org/10.1073/pnas.1008397107
Abstract
The development of cardiac hypertrophy in response to increased hemodynamic load and neurohormonal stress is initially a compensatory response that may eventually lead to ventricular dilation and heart failure. Regulator of G protein signaling 5 (Rgs5) is a negative regulator of G protein-mediated signaling by inactivating Gα(q) and Gα(i), which mediate actions of most known vasoconstrictors. Previous studies have demonstrated that Rgs5 expresses among various cell types within mature heart and showed high levels of Rgs5 mRNA in monkey and human heart tissue by Northern blot analysis. However, the critical role of Rgs5 on cardiac remodeling remains unclear. To specifically determine the role of Rgs5 in pathological cardiac remodeling, we used transgenic mice with cardiac-specific overexpression of human Rgs5 gene and Rgs5−/− mice. Our results demonstrated that the transgenic mice were resistant to cardiac hypertrophy and fibrosis through inhibition of MEK-ERK1/2 signaling, whereas the Rgs5−/− mice displayed the opposite phenotype in response to pressure overload. These studies indicate that Rgs5 protein is a crucial component of the signaling pathway involved in cardiac remodeling and heart failure.Keywords
This publication has 20 references indexed in Scilit:
- LIM and Cysteine-Rich Domains 1 Regulates Cardiac Hypertrophy by Targeting Calcineurin/Nuclear Factor of Activated T Cells SignalingHypertension, 2010
- Targeted Expression of Receptor-Associated Late Transducer Inhibits Maladaptive Hypertrophy via Blocking Epidermal Growth Factor Receptor SignalingHypertension, 2009
- RGS proteins: identifying new GAPs in the understanding of blood pressure regulation and cardiovascular functionClinical Science, 2009
- Generation and Characterization of rgs5 Mutant MiceMolecular and Cellular Biology, 2008
- Rgs5 Targeting Leads to Chronic Low Blood Pressure and a Lean Body HabitusMolecular and Cellular Biology, 2008
- Mediating ERK1/2 signaling rescues congenital heart defects in a mouse model of Noonan syndromeJCI Insight, 2007
- Overexpression of Myofibrillogenesis Regulator-1 Aggravates Cardiac Hypertrophy Induced by Angiotensin II in MiceHypertension, 2007
- ECM remodeling in hypertensive heart diseaseJCI Insight, 2007
- β adrenergic receptor-mediated atrial specific up-regulation of RGS5Life Sciences, 2005
- Pericyte‐specific expression ofRgs5:implications for PDGF and EDG receptor signaling during vascular maturationThe FASEB Journal, 2003