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.
Jason H. Rogers, Praveen Tamirisa, Attila Kovacs, Carla Weinheimer, Michael Courtois, Kendall J. Blumer, Daniel P. Kelly, Anthony J. Muslin
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International journal of molecular sciences | 2023 |
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International journal of molecular sciences | 2022 |
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American journal of physiology. Heart and circulatory physiology | 2012 |
An RGS4-Mediated Phenotypic Switch of Bronchial Smooth Muscle Cells Promotes Fixed Airway Obstruction in Asthma
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ML Martin, SL Belmonte, R Ram, FA Kamal, BC Blaxall |
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SP Heximer |
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The Critical Role of Astragalus Polysaccharides for the Improvement of PPRAα-Mediated Lipotoxicity in Diabetic Cardiomyopathy
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An RGS4-Mediated Phenotypic Switch of Bronchial Smooth Muscle Cells Promotes Fixed Airway Obstruction in Asthma
G Damera, KM Druey, PR Cooper, VP Krymskaya, RJ Soberman, Y Amrani, T Hoshi, CE Brightling, RA Panettieri, RE Morty |
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Identification of Transcription Factor E3 (TFE3) as a Receptor-independent Activator of Gα16
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Rescue of Cardiomyopathy in Peroxisome Proliferator-Activated Receptor-α Transgenic Mice by Deletion of Lipoprotein Lipase Identifies Sources of Cardiac Lipids and Peroxisome Proliferator-Activated Receptor-α Activators
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Regulation of GPCR signaling in Hypertension
HL Brinks, AD Eckhart |
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American journal of physiology. Heart and circulatory physiology | 2009 |
Activator of G protein signaling 8 (AGS8) is required for hypoxia-induced apoptosis of cardiomyocytes: role of G betagamma and connexin 43 (CX43)
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The Journal of biological chemistry | 2009 |
Breast cancer migration and invasion depend on proteasome degradation of regulator of G-protein signaling 4
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Cancer research | 2009 |
Uremic cardiac hypertrophy is reversed by rapamycin but not by lowering of blood pressure
AM Siedlecki, X Jin, AJ Muslin |
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BA Carabello, WJ Paulus |
The Lancet | 2009 |
Regulator of G Protein Signaling 5: A New Player in Vascular Remodeling
M Manzur, R Ganss |
Trends in Cardiovascular Medicine | 2009 |
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P Tornos, RO Bonow |
Valvular Heart Disease: A Companion to Braunwald's Heart Disease | 2009 |
Activator of G Protein Signaling 8 (AGS8) Is Required for Hypoxia-induced Apoptosis of Cardiomyocytes: ROLE OF Gβγ AND CONNEXIN 43 (CX43)
M Sato, Q Jiao, T Honda, R Kurotani, E Toyota, S Okumura, T Takeya, S Minamisawa, SM Lanier, Y Ishikawa |
The Journal of biological chemistry | 2009 |
Impaired contractile function and calcium handling in hearts of cardiac-specific calcineurin b1-deficient mice
PJ Schaeffer, J DeSantiago, J Yang, TP Flagg, A Kovacs, CJ Weinheimer, M Courtois, TC Leone, CG Nichols, DM Bers, DP Kelly |
American journal of physiology. Heart and circulatory physiology | 2009 |
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RGS5, RGS4, and RGS2 expression and aortic contractibility are dynamically co-regulated during aortic banding-induced hypertrophy
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Journal of Molecular and Cellular Cardiology | 2008 |
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A Gödecke, J Schrader, M Reinartz |
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Proceedings of the National Academy of Sciences | 2008 |
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Regulation of G protein-coupled receptor signalling: Focus on the cardiovascular system and regulator of G protein signalling proteins
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The FASEB Journal | 2008 |
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T Tasaki, YT Kwon |
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Journal of Hypertension | 2007 |
Phosphorylation of Ser166 in RGS5 by protein kinase C causes loss of RGS function
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Sphingosine-1-phosphate and endothelin-1 induce the expression of rgs16 protein in cardiac myocytes by transcriptional activation of the rgs16 gene
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B S??rm??n, R Skoumal, H Leskinen, J Rys??, M Ilves, Y Soini, J Tuukkanen, S Pikkarainen, Z Lak??-Fut??, B S??rm??n, L Papp, R deCh??tel, M T??th, H Ruskoaho, I Szokodi |
Journal of Hypertension | 2007 |
Glycogen Synthase Kinase-3α Reduces Cardiac Growth and Pressure Overload-induced Cardiac Hypertrophy by Inhibition of Extracellular Signal-regulated Kinases
P Zhai, S Gao, E Holle, X Yu, A Yatani, T Wagner, J Sadoshima |
The Journal of biological chemistry | 2007 |
Endogenous RGS proteins modulate SA and AV nodal functions in isolated heart: implications for sick sinus syndrome and AV block
Y Fu, X Huang, L Piao, AN Lopatin, RR Neubig |
American journal of physiology. Heart and circulatory physiology | 2007 |
Sphingosine-1-phosphate and endothelin-1 induce the expression of rgs16 protein in cardiac myocytes by transcriptional activation of the rgs16 gene.
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Naunyn-Schmiedeberg's Archives of Pharmacology | 2007 |
Inactivation of FAK in cardiomyocytes promotes cardiac eccentric hypertrophy and fibrosis in mice
Xu Peng, Marc S. Kraus, Huijun Wei, Tang-Long Shen, Romain Pariaut, Ana Alcaraz, Guangju Ji, Lihong Cheng, Qinglin Yang, Michael I. Kotlikoff, Ju Chen, Kenneth Chien, Hua Gu and Jun-Lin Guan |
Journal of Clinical Investigation | 2006 |
Intermittent Pressure Overload Triggers Hypertrophy-independent Cardiac Dysfunction and Vascular Rarefaction
Cinzia Perrino, Sathyamangla V. Naga Prasad, Lan Mao, Takahisa Noma, Zhen Yan, Hyung-Suk Kim, Oliver Smithies and Howard A. Rockman |
Journal of Clinical Investigation | 2006 |
Blocking cardiac growth in hypertrophic cardiomyopathy induces cardiac dysfunction and decreased survival only in males
SW Luckey, J Mansoori, K Fair, CL Antos, EN Olson, LA Leinwand |
American journal of physiology. Heart and circulatory physiology | 2006 |
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J Heineke, JD Molkentin |
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β-Catenin Overexpression Reduces Myocardial Infarct Size through Differential Effects on Cardiomyocytes and Cardiac Fibroblasts
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The Journal of biological chemistry | 2006 |
RGS2 is upregulated by and attenuates the hypertrophic effect of α1-adrenergic activation in cultured ventricular myocytes
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Proceedings of the National Academy of Sciences | 2005 |
Receptors, G Proteins, and Their Interactions
MW Hollmann, D Strumper, S Herroeder, ME Durieux |
Anesthesiology | 2005 |
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K Blumer |
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ZT Bloomgarden |
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Inactivation of 14-3-3 Protein Exacerbates Cardiac Hypertrophy and Fibrosis through Enhanced Expression of Protein Kinase C β2 in Experimental Diabetes
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N Wettschureck, S Offermanns |
Physiological reviews | 2005 |
Generation and Characterization of Rgs4 Mutant Mice
N Grillet, A Pattyn, C Contet, BL Kieffer, C Goridis, JF Brunet |
Molecular and cellular biology | 2005 |
G-protein signaling participates in the development of diabetic cardiomyopathy
IS Harris, I Treskov, MW Rowley, S Heximer, K Kaltenbronn, BN Finck, RW Gross, DP Kelly, KJ Blumer, AJ Muslin |
Diabetes | 2004 |
Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice
TC Leone, JJ Lehman, BN Finck, PJ Schaeffer, AR Wende, S Boudina, M Courtois, DF Wozniak, N Sambandam, C Bernal-Mizrachi, Z Chen, JO Holloszy, DM Medeiros, RE Schmidt, JE Saffitz, ED Abel, CF Semenkovich, DP Kelly |
Cell | 2004 |
Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice
TC Leone, JJ Lehman, BN Finck, PJ Schaeffer, AR Wende, S Boudina, M Courtois, DF Wozniak, N Sambandam, C Bernal-Mizrachi, Z Chen, JO Holloszy, DM Medeiros, RE Schmidt, JE Saffitz, ED Abel, CF Semenkovich, DP Kelly |
Cell | 2004 |
Genetic Factors in Cardiac Hypertrophy
GW Dorn, HS Hahn |
Annals of the New York Academy of Sciences | 2004 |
Adiponectin-mediated modulation of hypertrophic signals in the heart
R Shibata, N Ouchi, M Ito, S Kihara, I Shiojima, DR Pimentel, M Kumada, K Sato, S Schiekofer, K Ohashi, T Funahashi, WS Colucci, K Walsh |
Nature Medicine | 2004 |
Dominant negative 14-3-3 promotes cardiomyocyte apoptosis in early stage of type I diabetes mellitus through activation of JNK
N Gurusamy, K Watanabe, M Ma, S Zhang, AJ Muslin, M Kodama, Y Aizawa |
Biochemical and Biophysical Research Communications | 2004 |
Regulator of G protein signaling 5 marks peripheral arterial smooth muscle cells and is downregulated in atherosclerotic plaque
J Li, LD Adams, X Wang, L Pabon, SM Schwartz, DC Sane, RL Geary |
Journal of Vascular Surgery | 2004 |
Defects in RGS9 or its anchor protein R9AP in patients with slow photoreceptor deactivation
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 |