Paroxetine-mediated GRK2 inhibition reverses cardiac dysfunction and remodeling after myocardial infarction

Science Translational Medicine
Sarah M SchumacherWalter J Koch

Abstract

Heart failure (HF) is a disease of epidemic proportion and is associated with exceedingly high health care costs. G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR) kinase 2 (GRK2), which is up-regulated in the failing human heart, appears to play a critical role in HF progression in part because enhanced GRK2 activity promotes dysfunctional adrenergic signaling and myocyte death. Recently, we found that the selective serotonin reuptake inhibitor (SSRI) paroxetine could inhibit GRK2 with selectivity over other GRKs. Wild-type mice were treated for 4 weeks with paroxetine starting at 2 weeks after myocardial infarction (MI). These mice were compared with mice treated with fluoxetine, which does not inhibit GRK2, to control for the SSRI effects of paroxetine. All mice exhibited similar left ventricular (LV) dysfunction before treatment; however, although the control and fluoxetine groups had continued degradation of function, the paroxetine group had considerably improved LV function and structure, and several hallmarks of HF were either inhibited or reversed. Use of genetically engineered mice indicated that paroxetine was working through GRK2 inhibition. The beneficial effects of paroxetine we...Continue Reading

References

Jan 1, 1989·Acta Psychiatrica Scandinavica. Supplementum·T C TaskerC G Link
Jul 22, 1982·The New England Journal of Medicine·M R BristowE B Stinson
Jun 17, 1998·Proceedings of the National Academy of Sciences of the United States of America·H A RockmanW J Koch
May 2, 2001·Proceedings of the National Academy of Sciences of the United States of America·V B HardingH A Rockman
Jan 24, 2002·Nature·Howard A RockmanRobert J Lefkowitz
Aug 2, 2005·European Heart Journal·Guido IaccarinoWalter J Koch
Jun 27, 2006·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·H Kirchherr, W N Kühn-Velten
Feb 27, 2007·Nature Medicine·Anastasios LymperopoulosWalter J Koch
Jun 26, 2010·Circulation Research·Liam M CaseyBurns C Blaxall
Aug 7, 2010·Cleveland Clinic Journal of Medicine·Marc A Silver
Jan 24, 2012·Expert Opinion on Pharmacotherapy·Sara Gibiino, Alessandro Serretti
Jan 18, 2013·International Clinical Psychopharmacology·Chittaranjan AndradeSurya Sandarsh
Aug 31, 2013·Circulation Research·Anastasios LymperopoulosWalter J Koch
Apr 2, 2014·Mayo Clinic Proceedings·Shannon M DunlaySudhir S Kushwaha
Apr 8, 2014·Journal of the American College of Cardiology·Fadia A KamalBurns C Blaxall

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Citations

Feb 20, 2016·Journal of Computer-aided Molecular Design·Lucas N AlbercaAlan Talevi
Dec 9, 2015·Archives of Physiology and Biochemistry·Elisa LucasRocio Vila-Bedmar
Aug 19, 2015·Current Cardiology Reports·Peter A Shapiro
Jul 1, 2016·Journal of Medicinal Chemistry·Manuela GuccioneSilvana Grasso
Mar 4, 2017·Trends in Endocrinology and Metabolism : TEM·Qin FuYang K Xiang
May 18, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jonathan HullmannWalter J Koch
Jan 13, 2017·Cellular Signalling·Alessandro Cannavo, Walter J Koch
Nov 24, 2017·Expert Opinion on Therapeutic Targets·Alessandro CannavoGiuseppe Rengo
Jun 16, 2018·Basic & Clinical Pharmacology & Toxicology·Stefanie KlenkeUlrich H Frey
May 23, 2015·Circulation·Daniela Zablocki, Junichi Sadoshima
Nov 7, 2015·Circulation Research·Karen Patterson, Karen Patterson
Apr 2, 2016·Circulation Research·Joshua G TraversBurns C Blaxall
Mar 19, 2016·Circulation Research·Joshua G TraversBurns C Blaxall
Mar 23, 2017·Journal of Cardiovascular Pharmacology·Sarah M Schumacher, Walter J Koch
Feb 1, 2019·Expert Opinion on Therapeutic Targets·Melissa Lieu, Walter J Koch
Jul 18, 2019·Journal of Health Psychology·Alyson Pompeo-Fargnoli, Anthony S Fargnoli
Jul 23, 2015·Science Signaling·Rocio Vila-BedmarCristina Murga
Sep 27, 2019·Scientific Reports·Anup S PathaniaAnat Erdreich-Epstein
Jun 13, 2019·Nature Reviews. Cardiology·Jessica PflegerWalter J Koch
Dec 22, 2016·Frontiers in Cardiovascular Medicine·Daniela SorrientoGuido Iaccarino
Aug 1, 2019·Molecular and Cellular Biochemistry·Joann LagmanChristopher H So
May 22, 2020·Frontiers in Physiology·Xing FuLeshan Wang
Aug 28, 2020·Frontiers in Pharmacology·Natalia L Rukavina MikusicMariela M Gironacci
Aug 28, 2018·Frontiers in Pharmacology·Claudio de LuciaWalter J Koch
Dec 13, 2018·Frontiers in Pharmacology·Supachoke MangmoolHitoshi Kurose
Apr 3, 2019·International Journal of Molecular Sciences·Ersilia CipollettaGuido Iaccarino
May 16, 2019·The Journal of Experimental Medicine·Akiko NakaiKazuhiro Suzuki
Mar 29, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Melissa LieuWalter J Koch
Aug 31, 2016·International Journal of Molecular Medicine·Chen-Chen HanWei Wei
Dec 8, 2020·European Heart Journal·Rajika Roy, Walter J Koch

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