Loss of dynamic regulation of G protein-coupled receptor kinase 2 by nitric oxide leads to cardiovascular dysfunction with aging

Author:

Lieu Melissa1,Traynham Christopher J.1,de Lucia Claudio1,Pfleger Jessica1,Piedepalumbo Michela12,Roy Rajika1,Petovic Jennifer1,Landesberg Gavin3,Forrester Steven J.3,Hoffman Matthew1,Grisanti Laurel A.14,Yuan Ancai1,Gao Erhe1,Drosatos Konstantinos1,Eguchi Satoru3,Scalia Rosario3,Tilley Douglas G.1,Koch Walter J.1

Affiliation:

1. Center for Translational Medicine, Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania

2. Department of Medical, Surgical, Neurological, Metabolic, and Aging Sciences, University of Campania “Luigi Vanvitelli,” Naples, Italy

3. Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania

4. Department of Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, Missouri

Abstract

Research on G protein-coupled receptor kinase 2 (GRK2) in the setting of cardiovascular aging is largely unknown despite its strong established functions in cardiovascular physiology and pathophysiology. This study uses a mouse model of chronic GRK2 overactivity to further investigate the consequences of long-term GRK2 on cardiac function and structure. We report for the first time that chronic GRK2 overactivity was able to cause cardiac dysfunction and remodeling independent of surgical intervention, highlighting the importance of GRK activity in aged-related heart disease.

Funder

National Institute of Health

American Heart Association

Publisher

American Physiological Society

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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