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Cardiac Fibroblast GRK2 Deletion Enhances Contractility and Remodeling Following Ischemia/Reperfusion Injury

Authors :
Meryl C. Woodall
Ancai Yuan
Walter J. Koch
Erhe Gao
Benjamin P. Woodall
Source :
Circulation Research. 119:1116-1127
Publication Year :
2016
Publisher :
Ovid Technologies (Wolters Kluwer Health), 2016.

Abstract

Rationale: G protein–coupled receptor kinase 2 (GRK2) is an important molecule upregulated after myocardial injury and during heart failure. Myocyte-specific GRK2 loss before and after myocardial ischemic injury improves cardiac function and remodeling. The cardiac fibroblast plays an important role in the repair and remodeling events after cardiac ischemia; the importance of GRK2 in these events has not been investigated. Objective: The aim of this study is to elucidate the in vivo implications of deleting GRK2 in the cardiac fibroblast after ischemia/reperfusion injury. Methods and Results: We demonstrate, using Tamoxifen inducible, fibroblast-specific GRK2 knockout mice, that GRK2 loss confers a protective advantage over control mice after myocardial ischemia/reperfusion injury. Fibroblast GRK2 knockout mice presented with decreased infarct size and preserved cardiac function 24 hours post ischemia/reperfusion as demonstrated by increased ejection fraction (59.1±1.8% versus 48.7±1.2% in controls; P Conclusions: These novel data showing the benefits of inhibiting GRK2 in the cardiac fibroblast adds to previously published data showing the advantage of GRK2 ablation and reinforces the therapeutic potential of GRK2 inhibition in the heart after myocardial ischemia.

Details

ISSN :
15244571 and 00097330
Volume :
119
Database :
OpenAIRE
Journal :
Circulation Research
Accession number :
edsair.doi.dedup.....f8f7459f4ae285d4262d53ce36640945
Full Text :
https://doi.org/10.1161/circresaha.116.309538