Loss of dynamic regulation of G protein-coupled receptor kinase 2 by nitric oxide leads to cardiovascular dysfunction with aging
Melissa Lieu, Christopher J. Traynham, Claudio de Lucia, Jessica Pfleger, Michela Piedepalumbo, Rajika Roy, Jennifer Petovic, Gavin Landesberg, Steven J. Forrester, Matthew Hoffman, Laurel A. Grisanti, Ancai Yuan, Erhe Gao, Konstantinos Drosatos, Satoru Eguchi, Rosario Scalia, Douglas G. Tilley, Walter J. Koch
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.