Abstract 15486: Intramyocardial Gene Therapy With a Novel Angiogenic Molecule, Pellino-1 Preserves Functions and Increases Cell Survivability in a Mouse Myocardial Infarction Model
Introduction: Our present study attempted to evaluate the effect of Pellino1 (Peli1) overexpression on angiogenesis and myocardial function by intramyocardial administration of adenovirus encoding Peli1 (Ad.Peli1) following myocardial infarction (MI) in mice.
Methods: CD-1/ICR mice were divided into six groups: Control Sham (CS); Control MI (CMI); Adeno-LacZ Sham (Ad.LacZS); Adeno-LacZ MI (Ad.LacZMI); Adeno-Pellino1 Sham (Ad.Peli1S) and Adeno-Pellino1 MI (Ad.Peli1MI). MI was induced by permanent ligation of left anterior descending coronary artery (LAD). Following LAD ligation or sham surgery Ad.LacZ or Ad.Peli1 was injected at 4 border zone sites to either Ad.LacZS/Ad.LaczMI or Ad.Peli1S/Ad.Peli1MI groups respectively. Heart tissue was collected 24 hours post MI for Western blot analysis,4 days for gap junction protein and 30 days later for immunohistochemistry after echocardiographic analysis.
Results: Echocardiographic analysis revealed increased ejection fraction [48±0.75 vs. 33±0.98% (n=10-11);p<0.05] and fractional shortening [24±0.49 vs. 16±0.51% (n=10-11) p<0.05] along with decreased LVIDs [3.74±0.14 vs. 5.21±0.19(mm) (n=10-11); p<0.05] in the Ad.Peli1MI as compared to the Ad.LacZMI group. Immunohistochemical analysis for fibrosis with picrosirius red staining exhibited a decrease in collagen deposition in Ad.Peli1MI group [16±1.05 vs. 29±2.05% (n=8); p<0.0001] as compared to Ad.LacZMI group. Connexin-43, a major ventricular gap junction protein was found to be significantly expressed in Ad.Peli1MI group compared to Ad.LacZMI. Ad.Peli1 gene therapy after MI increased capillary density [2342±122 vs. 1776±54 counts/mm2 (n=6);p<0.05] as compared to the Ad.LacZMI group. Western blot analysis 24h after MI revealed increased phosphorylation of Akt (3.4 fold), eNOS (1.9fold) and MK2 (1.7fold) with Ad.Peli1 treatment compared to Ad.LacZ. Similar experiments conducted with Peli1KO mice also revealed decreased DNA binding activity of NFκB activity by Gel-shift analysis 8 h after MI.
Conclusion: Taken together, these data shows the potential of Peli1 gene therapy in inducing angiogenesis and reducing ventricular remodeling in the infarcted myocardium.
Author Disclosures: V. Coca-Soliz: None. L. Tapias: None. V. Selvaraju: None. M. Thirunavukkarasu: None. J. Palesty: None. N. Maulik: None.
- © 2014 by American Heart Association, Inc.