MCARD-Mediated Gene Transfer of GRK2 Inhibitor in Ovine Model of Acute Myocardial Infarction

β-Adrenergic receptor (βAR) dysfunction in acute myocardial infarction (MI) is associated with elevated levels of the G-protein-coupled receptor kinase-2 (GRK2), which plays a key role in heart failure progression. Inhibition of GRK2 via expression of a peptide βARKct transferred by molecular cardia...

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Veröffentlicht in:	Journal of cardiovascular translational research 2013-04, Vol.6 (2), p.253-262
Hauptverfasser:	Swain, JaBaris D., Fargnoli, Anthony S., Katz, Michael G., Tomasulo, Catherine E., Sumaroka, Marina, Richardville, Kyle C., Koch, Walter J., Rabinowitz, Joseph E., Bridges, Charles R.
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Biomedical Engineering and Bioengineering Biomedicine Cardiology Cardiomegaly - enzymology Cardiomegaly - genetics Cardiomegaly - pathology Cardiomegaly - therapy Dependovirus - genetics Disease Models, Animal G-Protein-Coupled Receptor Kinase 2 - antagonists & inhibitors G-Protein-Coupled Receptor Kinase 2 - biosynthesis G-Protein-Coupled Receptor Kinase 2 - genetics Gene Expression Regulation Gene Transfer Techniques Genetic Therapy Genetic Vectors Human Genetics Magnetic Resonance Imaging Male Medicine Medicine & Public Health Myocardial Contraction Myocardial Infarction - enzymology Myocardial Infarction - genetics Myocardial Infarction - pathology Myocardial Infarction - physiopathology Myocardial Infarction - therapy Myocardium - enzymology Myocardium - pathology Peptide Fragments - biosynthesis Peptide Fragments - genetics Receptors, Adrenergic, beta - metabolism Recovery of Function Sheep Stroke Volume Systole Time Factors Ventricular Function, Left Ventricular Pressure Ventricular Remodeling
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Zusammenfassung:	β-Adrenergic receptor (βAR) dysfunction in acute myocardial infarction (MI) is associated with elevated levels of the G-protein-coupled receptor kinase-2 (GRK2), which plays a key role in heart failure progression. Inhibition of GRK2 via expression of a peptide βARKct transferred by molecular cardiac surgery with recirculating delivery (MCARD) may be a promising intervention. Five sheep underwent scAAV6-mediated MCARD delivery of βARKct, and five received no treatment (control). After a 3-week period, the branch of the circumflex artery (OM1) was ligated. Quantitative PCR data showed intense βARKct expression in the left ventricle (LV). Circumferential fractional shortening was 23.4 ± 7.1 % (baseline) vs. −2.9 ± 5.2 % ( p
ISSN:	1937-5387 1937-5395 1937-5395
DOI:	10.1007/s12265-012-9418-z