| First Author | el Azzouzi H | Year | 2013 |
| Journal | Cell Metab | Volume | 18 |
| Issue | 3 | Pages | 341-54 |
| PubMed ID | 24011070 | Mgi Jnum | J:203819 |
| Mgi Id | MGI:5528778 | Doi | 10.1016/j.cmet.2013.08.009 |
| Citation | el Azzouzi H, et al. (2013) The hypoxia-inducible microRNA cluster miR-199a approximately 214 targets myocardial PPARdelta and impairs mitochondrial fatty acid oxidation. Cell Metab 18(3):341-54 |
| abstractText | Peroxisome proliferator-activated receptor delta (PPARdelta) is a critical regulator of energy metabolism in the heart. Here, we propose a mechanism that integrates two deleterious characteristics of heart failure, hypoxia and a metabolic shift toward glycolysis, involving the microRNA cluster miR-199a approximately 214 and PPARdelta. We demonstrate that under hemodynamic stress, cardiac hypoxia activates DNM3os, a noncoding transcript that harbors the microRNA cluster miR-199a approximately 214, which shares PPARdelta as common target. To address the significance of miR-199a approximately 214 induction and concomitant PPARdelta repression, we performed antagomir-based silencing of both microRNAs and subjected mice to biomechanical stress to induce heart failure. Remarkably, antagomir-treated animals displayed improved cardiac function and restored mitochondrial fatty acid oxidation. Taken together, our data suggest a mechanism whereby miR-199a approximately 214 actively represses cardiac PPARdelta expression, facilitating a metabolic shift from predominant reliance on fatty acid utilization in the healthy myocardium toward increased reliance on glucose metabolism at the onset of heart failure. |
