MCARD-mediated gene transfer of GRK2 inhibitor in ovine model of acute myocardial infarction

Jabaris D. Swain, Anthony S. Fargnoli, Michael G. Katz, Catherine E. Tomasulo, Marina Sumaroka, Kyle C. Richardville, Walter J. Koch, Joseph E. Rabinowitz, Charles R. Bridges

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


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 < 0.05) in the control at 10 weeks. In the MCARD-βARKct group, this parameter was close to baseline. The same trend was observed with LV wall thickening. Cardiac index fully recovered in the MCARD-βARKct group. LV end-diastolic volume and LV end-diastolic pressure did not differ in both groups. MCARD-mediated βARKct gene expression results in preservation of regional and global systolic function after acute MI without arresting progressive ventricular remodeling.

Original languageEnglish
Pages (from-to)253-262
Number of pages10
JournalJournal of Cardiovascular Translational Research
Issue number2
StatePublished - Apr 2013
Externally publishedYes


  • Acute myocardial infarction
  • Gene therapy
  • Molecular cardiac surgery
  • β-Adrenergic receptors


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