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Cardiac Fibroblast GRK2 Deletion Enhances Contractility and Remodeling Following Ischemia/Reperfusion Injury
- 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.
- Subjects :
- 0301 basic medicine
Cardiac function curve
Pathology
medicine.medical_specialty
G-Protein-Coupled Receptor Kinase 2
Physiology
Myocardial Ischemia
Myocardial Infarction
Ischemia
Myocardial Reperfusion Injury
030204 cardiovascular system & hematology
Second Messenger Systems
Article
Mice
03 medical and health sciences
0302 clinical medicine
Transduction, Genetic
Fibrosis
Internal medicine
Cyclic AMP
Animals
Medicine
RNA, Small Interfering
Fibroblast
Mice, Knockout
Ejection fraction
Tumor Necrosis Factor-alpha
business.industry
Myocardium
NF-kappa B
Heart
Stroke Volume
Cultural Diversity
Fibroblasts
medicine.disease
Myocardial Contraction
Rats
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Animals, Newborn
Gene Expression Regulation
Neutrophil Infiltration
Heart failure
Cardiology and Cardiovascular Medicine
business
Myofibroblast
Reperfusion injury
Subjects
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