Abstract
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.
Original language | English |
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Pages (from-to) | 341-354 |
Number of pages | 14 |
Journal | Cell Metabolism |
Volume | 18 |
Issue number | 3 |
DOIs | |
Publication status | Published - 3 Sept 2013 |
Keywords
- ACTIVATED RECEPTOR-DELTA
- CARDIAC-HYPERTROPHY
- HEART-FAILURE
- IN-VIVO
- ISCHEMIC-INJURY
- MOUSE HEART
- TWIST
- ANGIOGENESIS
- METASTASIS
- EXPRESSION