Abstract 16630: miR-92a Inhibition via LNA-92a is Cardioprotective After Acute Myocardial Infarction: Results of a Large Animal Model
miRNAs (miRs) are small non-coding RNAs, that posttranscriptionally regulate gene expression. Inhibition of miR-92a improved neovascularization in chronic ischemia and reduced infarct size after LAD occlusion in mice. To determine whether inhibition of miR-92a might be useful to treat ischemic diseases, we performed a pre-clinical study in pigs.
Methods: Pigs (n=5/group) underwent percutaneous LAD occlusion for 60 min followed by 72 hours of reperfusion. Locked nucleic acid-modified anti-sense miR-92a (LNA-92a; 5 mg/kg heart weight) was applied at the end of LAD occlusion either regional or systemic. Reduction of target RNA was analyzed via qPCR. Left ventricular enddiastolic pressure (LVEDP), regional myocardial function and infarct size were measured at day 3. A 5-fold increased concentration of LNA-92a was applied locally to determine optimal treatment concentration. Regional inflammation was measured via myeloperoxidaxe assay.
Results: Locked nuleic acid-modified anti-sense miR-92a significantly reduced miR-92a expression in the heart. Regional LNA-92a application reduced the infarct size, systemic application of LNA-92a showed less profound effect. Increased LNA concentration did not further reduce the infarct size. Moreover, LVEDP increase was reduced after regional miRNA-92a inhibition, whereas i.v. injection was not sufficient to considerably reduce LVEDP. In addition, regional myocardial function (subendocardial segment shortening, SES) revealed similar results. Analysis of the MPO as an indicator of inflammatory cell invasion showed a significant reduction in the LNA-92a-treated pigs. (Table 1,* p<0.05 vs. control)
Conclusion: Regional reduction of miR-92a levels via LNA-92a is cardioprotective in a pig model of ischemia/reperfusion injury. These suggests, that miR-92a inhibition might be a novel therapeutic tool to augment cardiac function after ischemia.
- © 2013 by American Heart Association, Inc.