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Improving Left Ventricular Function And Angiogenesis After MI In Flk Knock Out Mice With Intramyocardial Gene Therapy With Pellino1, a Novel Molecule In VEGF Signaling Pathway
*Ibnalwalid Saad1,2, *Mahesh Thirunavukkarasu2, *Vladimir Coca-Soliz1, *Vathinathen Selvaraju2, J. Alexander Palesty1, *Nilanjana Maulik2 1Saint Mary's Hospital, Waterbury, CT;2University of Connecticut Health, Farmington, CT
Objective: In the present study we attempted to see whether Peli1 gene therapy can rescue disruption of cardioprotection and angiogenesis in Flk-1+/- mice subjected to MI Design: A preclincal animal study, duration of follow up is 30 days Setting: Molecular Cardiology and Angiogenesis Laboratory; University Research Facility Patients: Flk-1+/- mice in two groups: 1-Ad.Peli1MI and 2-Ad.LacZMI. Interventions: Flk+/- mice underwent MI by ligation of left anterior descending coronary artery(LAD). Following LAD ligation surgery mice were treated by either intramyocardial adenopellino1(Ad.Peli1MI) or adenoLacz(Ad.LacZMI). Main Outcome Measures: Echocardiographic analysis was performed preoperatively and on postoperative day 30. Heart tissue was collected on postoperative day 30 for immunohistochemistry(IHC) to measure capillary density and fibrosis. Results: Echocardiogram revealed increased EF [45% ± 1.46 vs. 24% ± 0.87 (n=9-11); p<0.05] and FS [23% ± 0.86 vs. 11% ± 0.45 (n=9-11); p<0.05)] along with decreased LVIDs [4.2 mm ± 0.16 vs. 5.4 mm ± 0.22 (n=9-11; p<0.05)] in Ad.Peli1MI group as compared to Ad.LacZMI. Vessel density staining showed increased number of capillaries in the Ad.Peli1MI group [2408 ± 60.45 vs. 2011 ± 112.4 (counts/mm2, n=6-7; p<0.05)] as compared to Ad.LacZMI. Also IHC for fibrosis exhibited decreased collagen deposition in Ad.Peli1MI group [7% ± 0.44 vs. 14% ± 0.39 (n=7-11); p<0.05] as compared to Ad.LacZMI. Conclusions: Peli1 gene therapy can promote angiogenesis, diminish cardiac fibrosis, and improve myocardial function in Flk1+/- mice subjected to MI. These findings have great clincal potential for future therapy in humans as a powerful tool to assist in injured myocardial tissue recovery following an MI.
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