MCARD-mediated gene transfer of GRK2 inhibitor in ovine model of acute myocardial infarction.
J Cardiovasc Transl Res
; 6(2): 253-62, 2013 Apr.
Article
in En
| MEDLINE
| ID: mdl-23208013
ABSTRACT
ß-Adrenergic receptor (ßAR) 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 ßARKct transferred by molecular cardiac surgery with recirculating delivery (MCARD) may be a promising intervention. Five sheep underwent scAAV6-mediated MCARD delivery of ßARKct, 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 ßARKct expression in the left ventricle (LV). Circumferential fractional shortening was 23.4 ± 7.1 % (baseline) vs. -2.9 ± 5.2 % (p < 0.05) in the control at 10 weeks. In the MCARD-ßARKct group, this parameter was close to baseline. The same trend was observed with LV wall thickening. Cardiac index fully recovered in the MCARD-ßARKct group. LV end-diastolic volume and LV end-diastolic pressure did not differ in both groups. MCARD-mediated ßARKct gene expression results in preservation of regional and global systolic function after acute MI without arresting progressive ventricular remodeling.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptide Fragments
/
Genetic Therapy
/
Gene Transfer Techniques
/
G-Protein-Coupled Receptor Kinase 2
/
Myocardial Infarction
/
Myocardium
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Cardiovasc Transl Res
Journal subject:
ANGIOLOGIA
/
CARDIOLOGIA
Year:
2013
Document type:
Article
Affiliation country: