betaARKct: a therapeutic approach for improved adrenergic signaling and function in heart disease.

Journal of Cardiovascular Translational Research
Henriette Brinks, W J Koch

Abstract

One of the most powerful regulators of cardiovascular function is catecholamine-stimulated adrenergic receptor (AR) signaling. The failing heart is characterized by desensitization and impaired beta-AR responsiveness as a result of upregulated G protein-coupled receptor kinase-2 (GRK2) present in injured myocardium. Deterioration of cardiac function is progressively enhanced by chronic adrenergic over-stimulation due to increased levels of circulating catecholamines. Increased GRK2 activity contributes to this pathological cycle of over-stimulation but lowered responsiveness. Over the past two decades the GRK2 inhibitory peptide betaARKct has been identified as a potential therapy that is able to break this vicious cycle of self-perpetuating deregulation of the beta-AR system and subsequent myocardial malfunction, thus halting development of cardiac failure. The betaARKct has been shown to interfere with GRK2 binding to the betagamma subunits of the heterotrimeric G protein, therefore inhibiting its recruitment to the plasma membrane that normally leads to phosphorylation and internalization of the receptor. In this article we summarize the current data on the therapeutic effects of betaARKct in cardiovascular disease and repor...Continue Reading

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Citations

Jul 28, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Christina A Pacak, Barry J Byrne
Jul 23, 2011·Circulation Research·Stephen L Belmonte, Burns C Blaxall
Jul 29, 2011·International Journal of Cardiology·George E Louridas, Katerina G Lourida
Dec 4, 2014·Lancet·Eugene Braunwald
Aug 31, 2013·Circulation Research·Sven T PlegerPatrick Most
Feb 18, 2014·PloS One·Chao ChengJiahong Xia
Jul 18, 2014·PloS One·Neeta AdhikariJennifer L Hall
Jul 20, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Mikiko OhnoEiichiro Nishi

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