Myocardial beta1-adrenergic receptor polymorphisms affect functional recovery after ischemic injury

American Journal of Physiology. Heart and Circulatory Physiology
Shahab A AkhterS B Liggett

Abstract

Association studies suggest beta(1)-adrenergic receptor (beta(1)-AR) polymorphisms are disease modifiers in heart failure. The Arg389 variant has increased coupling to G(s) in transfected cells and evokes enhanced ventricular function in transgenic mice. Here, we assessed the differential effects of the human Gly389 and Arg389 beta(1)-AR polymorphisms on myocardial recovery after ischemic injury. Function was studied in transgenic mice with cardiac-specific expression of either human Gly389 or Arg389 beta(1)-AR at baseline and after 20 min of ex vivo ischemia and reperfusion (I/R). In 3-mo-old mice of either genotype, there was poor recovery after I/R (approximately 38% vs. approximately 68% for nontransgenic). Paradoxically, at 6 mo of age, functional recovery remained severely depressed in Gly389 hearts (approximately 32%) but was similar to nontransgenic for Arg389 hearts (approximately 60%). In Arg389 hearts, agonist-promoted adenylyl cyclase activities were depressed by approximately 35% at 6 mo of age, and G protein-coupled receptor kinase (GRK) activity was increased by approximately twofold compared with Gly389. Furthermore, I/R evoked an approximately threefold increase in ERK2 phosphorylation in Arg389 but an approxim...Continue Reading

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Citations

Mar 3, 2010·The Journal of Biological Chemistry·Ricky MalhotraShahab A Akhter
May 29, 2009·Clinical and Experimental Pharmacology & Physiology·Eiji ToyotaKiyoshi Yoshida
Sep 22, 2010·Molecular Pharmacology·Chetan B PatelHoward A Rockman
Feb 22, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Ricky MalhotraShahab A Akhter
Sep 19, 2006·American Journal of Respiratory Cell and Molecular Biology·Steven M SwiftStephen B Liggett
Jan 4, 2007·The Journal of Clinical Investigation·Brent R DeGeorge, Walter J Koch
Mar 12, 2008·Journal of Translational Medicine·Michael A PacanowskiJulie A Johnson
May 20, 2008·The Journal of Urology·Matthew N SimmonsInderbir S Gill
Mar 13, 2016·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·JoAnn LindenfeldMichael R Bristow
Dec 26, 2007·European Journal of Heart Failure·Amal MuthumalaSteve E Humphries
Apr 26, 2007·Circulation Journal : Official Journal of the Japanese Circulation Society·Eiji ToyotaKiyoshi Yoshida
Mar 16, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Sven T Pleger, Walter J Koch
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Jul 2, 2021·Saudi Pharmaceutical Journal : SPJ : the Official Publication of the Saudi Pharmaceutical Society·Khaled AlhosainiF Al-Zoghaibi
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Mar 6, 2010·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Shahab A AkhterValluvan Jeevanandam

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