The Hypoxia-Inducible MicroRNA Cluster miR-199a similar to 214 Targets Myocardial PPAR delta and Impairs Mitochondrial Fatty Acid Oxidation

Peroxisome proliferator-activated receptor delta (PPARdelta) is a regulator of energy metabolism in the heart. Here, we propose a integrates two deleterious characteristics of heart failure, hypoxia and metabolic shift toward glycolysis, involving the microRNA cluster miR- approximately 214 and PPARdelta. We demonstrate that under hemodynamic cardiac hypoxia activates DNM3os, a noncoding transcript that harbors microRNA cluster miR-199a approximately 214, which shares PPARdelta as target. To address the significance of miR-199a approximately 214 concomitant PPARdelta repression, we performed antagomir-based silencing microRNAs and subjected mice to biomechanical stress to induce heart Remarkably, antagomir-treated animals displayed improved cardiac restored mitochondrial fatty acid oxidation. Taken together, our data mechanism whereby miR-199a approximately 214 actively represses cardiac expression, facilitating a metabolic shift from predominant reliance on acid utilization in the healthy myocardium toward increased reliance on metabolism at the onset of heart failure.