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

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 following 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 (I/R) 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 I/R injury. Fibroblast GRK2 knockout mice presented with decreased infarct size and preserved cardiac function 24 hours post-I/R as demonstrated by increased ejection fraction (58.1±1.8% vs. 48.7±1.2% in controls, p