P155Targeting myocardial edema: The depletion of extracellular RNA reduces vascular permeability and myocardial infarction size

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Abstract

Cell injury resulting from myocardial infarction (MI) leads to exposureof intracellular material and is associated with increased permeability ofvessels in the vicinity of the damage, a process that contributes to tissueinjury throughout the ventricle. As previously demonstrated by our group,released, natural extracellular RNA significantly increases the permeability acrossmicrovascular endothelial cells through a vascular endothelial growth factor(VEGF)-dependent mechanism. In the present study we thereforeevaluated changes of vascular permeability, edema formation andmyocardial infarction size following a depletion ofextracellular RNA after in vivoinduction of MI .

The leftcoronary artery (LAD) of C57/Bl 6 mice was ligated and RNase (100μg) or controlbuffer was administered intravenously 30 min, 3 and 6 hours following LADligation. Wet and dry weight of heart slices were measuerd for analysis ofmyocardial edema, and evans blue dye and tetrazolium were used to delineate thearea at risk and infarction size within the myocardium 24h after ligation.Cardiac function as measured by fractional shortening was assessed byechocardiography. Water content of myocardial tissue and myocardial perfusionwas calculated by wet/dry-ratio or micro-CT-Imaging respectively.

RNAsetreatment had no effect on blood pressure, total plasma protein or albuminlevels, peripheral blood cell counts or glucose levels. However, edemaformation was significantly decreased in RNAse treated mice as measured bywet/dry ratio (3.38 ± 0.19 vs. 3.93 + - 0.27; P < 0.05). Assessment of myocardial perfusion by micro-CTangiography revealed a significantly increased perfusion of the peri-infarct zone.Since risk zone sizes were similar between groups, the percentageinfarction of the risk zone was significantly smaller in RNAsetreated mice (P < 0.05). Left ventricular function as assessed by echocardiography and fractionalshortening analysis was significantly enhanced in RNAse treated mice (25.3 ± 2.6% vs. 13.8 ± 2.6 %; P < 0.05). Consequentelythe application of RNAse led to a significant increase of survival of mice following MI hier noch zahlen, Ns und P einfügen …

These results identify extracellular RNA as a novel natural permeabilityfactor which augments ischemia-induced edema formation and myocardialinfarction. Moreover, RNase treatment serving as a novel vessel-protectivemodality, prevents MI-induced edema formation and tissue injury and thussignificantly improves survival following MI.

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