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

H. El Azzouzi, S. Leptidis, E. Dirkx, J. Hoeks, B. van Bree, K van de Brand, E.A. McClellan, E. Poels, J.C. Sluimer, M.M. van den Hoogenhof, A.S. Armand, X. Yin, S. Langley, M. Bourajjaj, S. Olieslagers, J. Krishnan, M. Vooijs, H. Kurihara, A. Stubbs, Y.M. PintoW. Krek, M. Mayr, P.A. da Costa Martins, P. Schrauwen, L.J. De Windt*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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 languageEnglish
Pages (from-to)341-354
Number of pages14
JournalCell Metabolism
Volume18
Issue number3
DOIs
Publication statusPublished - 3 Sep 2013

Keywords

  • ACTIVATED RECEPTOR-DELTA
  • CARDIAC-HYPERTROPHY
  • HEART-FAILURE
  • IN-VIVO
  • ISCHEMIC-INJURY
  • MOUSE HEART
  • TWIST
  • ANGIOGENESIS
  • METASTASIS
  • EXPRESSION

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