Abstract 20299: Depletion of Extracellular RNA Improves Survival after Myocardial Infarction Reducing Vascular Permeability, Edema Formation and Myocardial Tissue Damage
Cell injury following myocardial infarction (MI) leads to the exposure of intracellular material and is associated with increased permeability of vessels in the vicinity of the damage. This process contributes to tissue injury throughout the ventricle. We previously demonstrated that released, natural extracellular RNA (eRNA) significantly increased the permeability across microvascular endothelial cells via vascular endothelial growth factor (VEGF)-dependent mechanisms. Here we evaluate changes of vascular permeability, edema formation and MI-size following a depletion of eRNA after in vivo induction of MI. The left coronary artery (LAD) of C57/Bl 6 mice was ligated and RNase or control buffer was administered intravenously 30 min, 3 and 6 hrs following LAD-ligation. Wet and dry weights of heart slices were measured for analysis of myocardial edema. Evans blue dye and tetrazolium were used to delineate the area at risk- (AAR) and infarction size within the myocardium 24h after ligation. Cardiac function, measured by fractional shortening (fs), was assessed by echocardiography. Water content of myocardial tissue and myocardial perfusion (MP) was calculated by wet/dry-ratio or Micro-CT-Imaging, respectively. RNAse treatment did not effect blood pressure, total plasma protein or albumin levels, peripheral blood cell counts or glucose levels. However, edema formation was significantly decreased in RNAse treated mice as measured by wet/dry ratio (3.38 ± 0.19 vs. 3.93 ± 0.27; P<0.05). Calculating MP by micro-CT angiography we detected a significantly increased perfusion of the peri-infarct zone. Since AAR-sizes were similar between groups, the percentage infarction of the AAR was significantly smaller in RNAse treated mice (P<0.05). Left ventricular function as assessed by echocardiography and fs analysis was significantly enhanced in RNAse treated mice (25.3 ± 2.6% vs. 13.8 ± 2.6 %; P<0.05). Consequentely the application of RNAse significantly increased survival of mice following MI (38.2 ± 2.1% vs 63.2±2.9%, n=8, p< 0.05). Thus targeting eRNA as a novel natural permeability factor reduces ischemia-induced myocardial edema formation and tissue injury and hence significantly improves survival following MI.
- © 2010 by American Heart Association, Inc.