374 cornoary sinus delivery of SDF 1 plasmid improves cardiac function in a porcine model of heart failure

374 Cornoary Sinus Delivery of SDF 1 Plasmid Improves Cardiac Function in a Porcine Model of Heart Failure Molecular Therapy Volume 22, Supplement 1, May 2014 Copyright © The American Society of Gene[.]

CARDIOVASCULAR AND PULMONARY DISEASES I 373 Intramyocardial Delivery of scAAV9 S100A1 in an Ischemic Rodent Model Results in Accentuated Changes in Cardiomyocyte Energetics through Increased Mitochondrial Oxidative Phosphorylation Activity Richard D Williams,1 Michael G Katz,1 Anthony S Fargnoli,1 Anna V Ivanina,2 Inna M Sokolova,2 Charles R Bridges.1 Carolinas HealthCare System, Charlotte, NC; 2University of North Carolina at Charlotte, Charlotte, NC Background S100A1 is a Ca2+-sensing protein of the EF-hand type and a positive inotropic regulator of myocardial function S100A1’s therapeutic actions in cardiomyocytes are attributed to increased sarcoplasmic reticulum activity, diminished diastolic Ca2+ leak, and augmented systolic open probability of the ryanodine receptor, causing an overall gain in SR Ca2+ cycling Moreover, S100A1 also is known to have multiple binding targets within the mitochondria Interaction with these targets is believed to enhance the mitochondrial energy and increase cytosolic ATP Numerous studies have demonstrated that S100A1 overexpression is therapeutically efficacious, yet the mechanistic details remain elusive, especially with regard to mitochondrial oxidative phosphorylative capacity Here we evaluate the role of S100A1 on mitochondrial energetics Methods Male Sprague-Dawley rats (N=18) were divided into groups: 1) naive animals (NAÏVE, n=7); 2) myocardial infarction (MI) with intramyocardial (IM) saline injection (MI/SALINE, n=6); 3) MI with IM injection of 1.2x1011 gc AAV9.S100A1 (MI/S100A1, n=5) In the (MI/SALINE) and (MI/S100A1) groups, animals received 300μL of either saline or AAV9.S100A1 solution via three left ventricular injections, immediately followed by ligation of the proximal left anterior descending artery Echocardiograms were performed at ten weeks post infarction Mitochondria were isolated from a tissue zone remote to the infarct and then evaluated for phosphorylative capacity, proton leak, and respiratory control ratio (RCR+) Results Ten weeks after infarction, significant adverse remodeling was observed in all non-(NAIVE) rats RCR+ was significantly decreased in (MI/SALINE) compared to (NAIVE) (1.66±0.09 vs 2.19±0.20, p0.05, Fig A) In both (MI/S100A1) and (MI/SALINE), ejection fraction (EF), end systolic volume (ESV) and end diastolic volume (EDV) were significantly altered compared to (NAIVE), all p