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Citations to this article

RGS4 causes increased mortality and reduced cardiac hypertrophy in response to pressure overload
Jason H. Rogers, … , Daniel P. Kelly, Anthony J. Muslin
Jason H. Rogers, … , Daniel P. Kelly, Anthony J. Muslin
Published September 1, 1999
Citation Information: J Clin Invest. 1999;104(5):567-576. https://doi.org/10.1172/JCI6713.
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Article

RGS4 causes increased mortality and reduced cardiac hypertrophy in response to pressure overload

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Abstract

RGS family members are GTPase-activating proteins (GAPs) for heterotrimeric G proteins. There is evidence that altered RGS gene expression may contribute to the pathogenesis of cardiac hypertrophy and failure. We investigated the ability of RGS4 to modulate cardiac physiology using a transgenic mouse model. Overexpression of RGS4 in postnatal ventricular tissue did not affect cardiac morphology or basal cardiac function, but markedly compromised the ability of the heart to adapt to transverse aortic constriction (TAC). In contrast to wild-type mice, the transgenic animals developed significantly reduced ventricular hypertrophy in response to pressure overload and also did not exhibit induction of the cardiac “fetal” gene program. TAC of the transgenic mice caused a rapid decompensation in most animals characterized by left ventricular dilatation, depressed systolic function, and increased postoperative mortality when compared with nontransgenic littermates. These results implicate RGS proteins as a crucial component of the signaling pathway involved in both the cardiac response to acute ventricular pressure overload and the cardiac hypertrophic program.

Authors

Jason H. Rogers, Praveen Tamirisa, Attila Kovacs, Carla Weinheimer, Michael Courtois, Kendall J. Blumer, Daniel P. Kelly, Anthony J. Muslin

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KM Nishiguchi, MA Sandberg, AC Kooijman, KA Martemyanov, JW Pott, SA Hagstrom, VY Arshavsky, EL Berson, TP Dryja
Nature 2004
Transgenic Models in Pharmacology
S Offermanns, L Hein
2004
Inhibition of Phenylephrine-Induced Cardiomyocyte Hypertrophy by Activation of Multiple Adenosine Receptor Subtypes
XT Gan, V Rajapurohitam, JV Haist, P Chidiac, MA Cook, M Karmazyn
The Journal of pharmacology and experimental therapeutics 2004
Hypertension and prolonged vasoconstrictor signaling in RGS2-deficient mice
Scott P. Heximer, Russell H. Knutsen, Xiaoguang Sun, Kevin M. Kaltenbronn, Man-Hee Rhee, Ning Peng, Antonio Oliveira-dos-Santos, Josef M. Penninger, Anthony J. Muslin, Thomas H. Steinberg, J. Michael Wyss, Robert P. Mecham, Kendall J. Blumer
Journal of Clinical Investigation 2003
The Role of the Grb2-p38 MAPK Signaling Pathway in Cardiac Hypertrophy and Fibrosis
Shaosong Zhang, Carla Weinheimer, Michael Courtois, Attila Kovacs, Cindy E. Zhang, Li Ye, Alec M. Cheng, Yibin Wang, Anthony J. Muslin
Journal of Clinical Investigation 2003
Developmental Adaptation of the Mouse Cardiovascular System to Elastin Haploinsufficiency
Gilles Faury Mylène Pezet Russell H. Knutsen Walter A. Boyle Scott P. Hexamer Sean E. McLean Robert K. Minkes Kendall J. Blumer Attila Kovacs Daniel P. Kelly Dean Y. Li Barry Starcher Robert P. Mecham
Journal of Clinical Investigation 2003
The aorta and heart differentially express RGS (regulators of G-protein signalling) proteins that selectively regulate sphingosine 1-phosphate, angiotensin II and endothelin-1 signalling
H Cho, K Harrison, O Schwartz, JH Kehrl
Biochemical Journal 2003
Pericyte‐specific expression of Rgs5: implications for PDGF and EDG receptor signaling during vascular maturation
H Cho, T Kozasa, C Bondjers, C Betsholtz, JH Kehrl
The FASEB Journal 2003
C ARDIAC H YPERTROPHY : The Good, the Bad, and the Ugly
N Frey, EN Olson
Annual Review of Physiology 2003
A critical role for PPARalpha-mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy: modulation by dietary fat content
BN Finck, X Han, M Courtois, F Aimond, JM Nerbonne, A Kovacs, RW Gross, DP Kelly
Proceedings of the National Academy of Sciences 2003
CARDIACHYPERTROPHY: The Good, the Bad, and the Ugly
N Frey, EN Olson
Annual Review of Physiology 2003
Molecular interplay between mechanical and humoral signalling in cardiac hypertrophy
G Tarone, G Lembo
Trends in Molecular Medicine 2003
Dual roles of modulatory calcineurin-interacting protein 1 in cardiac hypertrophy
RB Vega, BA Rothermel, CJ Weinheimer, A Kovacs, RH Naseem, R Bassel-Duby, RS Williams, EN Olson
Proceedings of the National Academy of Sciences 2003
Regulators of G-protein signalling: multifunctional proteins with impact on signalling in the cardiovascular system
T Wieland, C Mittmann
Pharmacology & Therapeutics 2003
Vascular failure: A hypothesis
SM Schwartz, RL Geary, LD Adams
Current Atherosclerosis Reports 2003
Cardiac hypertrophy and altered β-adrenergic signaling in transgenic mice that express the amino terminus of β-ARK1
JR Keys, EA Greene, CJ Cooper, SV Prasad, HA Rockman, WJ Koch
American journal of physiology. Heart and circulatory physiology 2003
Hypertension and prolonged vasoconstrictor signaling in RGS2-deficient mice
SP Heximer, RH Knutsen, X Sun, KM Kaltenbronn, MH Rhee, N Peng, A Oliveira-dos-Santos, JM Penninger, AJ Muslin, TH Steinberg, JM Wyss, RP Mecham, KJ Blumer
Journal of Clinical Investigation 2003
Activity, Regulation, and Intracellular Localization of RGS Proteins
P Chidiac, AA Roy
Receptors and Channels 2003
Shedding growth factors in cardiac hypertrophy
JK Liao
Nature Medicine 2002
Cardiac Structure and Function in Young and Senescent Mice Heterozygous for a Connexin43 Null Mutation
T Betsuyaku, A Kovacs, JE Saffitz, KA Yamada
Journal of Molecular and Cellular Cardiology 2002
Down-regulation of acyl-CoA oxidase gene expression and increased NF-κB activity in etomoxir-induced cardiac hypertrophy
À Cabrero, M Merlos, JC Laguna, MV Carrera
Journal of lipid research 2002
Expression Profiling Identifies 147 Genes Contributing to a Unique Primate Neointimal Smooth Muscle Cell Phenotype
RL Geary, JM Wong, A Rossini, SM Schwartz, LD Adams
Arteriosclerosis, thrombosis, and vascular biology 2002
A novel mouse model of lipotoxic cardiomyopathy
Hsiu-Chiang Chiu, Attila Kovacs, David A. Ford, Fong-Fu Hsu, Ricardo Garcia,Pilar Herrero, Jeffrey E. Saffitz, Jean E. Schaffer
Journal of Clinical Investigation 2001
Statins as Antioxidant Therapy for Preventing Cardiac Myocyte Hypertrophy
Masao Takemoto, Koichi Node, Hironori Nakagami, Yulin Liao, Michael Grimm, Yaeko Takemoto, Masafumi Kitakaze, James K. Liao
Journal of Clinical Investigation 2001
The in vivo role of p38 MAP kinases in cardiac remodeling and restrictive cardiomyopathy
P Liao, D Georgakopoulos, A Kovacs, M Zheng, D Lerner, H Pu, J Saffitz, K Chien, RP Xiao, DA Kass, Y Wang
Proceedings of the National Academy of Sciences 2001
Cytoplasmic signaling pathways that regulate cardiac hypertrophy
JD Molkentin, GW 2nd
Annual Review of Physiology 2001
RGS4 reduces contractile dysfunction and hypertrophic gene induction in Galpha q overexpressing mice
JH Rogers, A Tsirka, A Kovacs, KJ Blumer, GW 2nd, AJ Muslin
Journal of Molecular and Cellular Cardiology 2001
RGS Proteins to the Rescue
PH Sugden
Journal of Molecular and Cellular Cardiology 2001
Primary Myopathy and Accumulation of PrPSc-Like Molecules in Peripheral Tissues of Transgenic Mice Expressing a Prion Protein Insertional Mutation
R Chiesa, A Pestronk, RE Schmidt, WG Tourtellotte, B Ghetti, P Piccardo, DA Harris
Neurobiology of Disease 2001
Profile of RGS expression in single rat atrial myocytes
CA Doupnik, T Xu, JM Shinaman
Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression 2001
Functional expression of a GFP-tagged Kv1.5 α-subunit in mouse ventricle
H Li, W Guo, H Xu, R Hood, AT Benedict, JM Nerbonne
American journal of physiology. Heart and circulatory physiology 2001
G-proteins in growth and apoptosis: lessons from the heart
JW Adams, JH Brown
Oncogene 2001
Deactivation of the peroxisome proliferation-activated receptor alpha during cardiac myocyte hypertrophic growth
Philip M. Barger, Jon M. Brandt, Teresa C. Leone, Carla J. Weinheimer, Daniel P. Kelly
Journal of Clinical Investigation 2000
Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) promotes cardiac mitochondrial biogenesis
John J. Lehman, Philip M. Barger, Attila Kovacs, Jeffrey E. Saffitz, Denis Medeiros, Daniel P. Kelly
Journal of Clinical Investigation 2000
FROM THESARCOMERE TO THENUCLEUS: Role of Genetics and Signaling in Structural Heart Disease
RL Nicol, N Frey, EN Olson
Annual Review of Genomics and Human Genetics 2000
14-3-3 proteins block apoptosis and differentially regulate MAPK cascades
H Xing, S Zhang, C Weinheimer, A Kovacs, AJ Muslin
The EMBO Journal 2000
Regulators of G-protein Signaling in Receptor Complexes
DA Sierra, S Popov, TM Wilkie
Trends in Cardiovascular Medicine 2000
A Comparison of Aorta and Vena Cava Medial Message Expression by cDNA Array Analysis Identifies a Set of 68 Consistently Differentially Expressed Genes, All in Aortic Media
LD Adams, RL Geary, B McManus, SM Schwartz
Circulation research 2000
Calcineurin and Beyond: Cardiac Hypertrophic Signaling
JD Molkentin
Circulation research 2000
DNA wrapping and bending by a mitochondrial high mobility group-like transcriptional activator protein
JJ Lehman, PM Barger, A Kovacs, JE Saffitz, DM Medeiros, DP Kelly
Journal of Clinical Investigation 1992

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