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microRNA expression and its potential role in cardioprotection by ischemic postconditioning in pigs

  • Molecular and cellular mechanisms of disease
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

Ischemic postconditioning (PoCo) reduces infarct size following myocardial ischemia/reperfusion. To protect, PoCo must be performed early during reperfusion, and causal cardioprotective signaling must occur then. The role of microRNA (miRNA) in PoCo is unclear. Anesthetized pigs were subjected to 60 min left anterior descending coronary artery (LAD) occlusion and 180 min reperfusion. Immediate full reperfusion (IFR, n = 5) was compared to PoCo (four cycles of 60 s/60 s reperfusion/reocclusion, n = 5). Transmural myocardial biopsies from the LAD territory were sampled at baseline, 60 min ischemia, 10 and 180 min reperfusion. RNA was isolated. The expression of 11 miRNAs, including muscle-specific (miRNA-1, -133a, -206, -208b, -214, and -499), fibrosis- (miRNA-21, -24, and -29b), neovascularization- (miRNA-92a), and inflammation-associated (miRNA-146b) candidates, was quantified using real-time PCR (RT-PCR). mRNA expression at baseline and 180 min reperfusion was quantified and validated (microarray and RT-PCR). PoCo reduced infarct size from 44.9 ± 7.7 to 34.8 ± 5.3 % of the area at risk. The expression of miRNA-1, -24, -29b, -133a, -146b, -208b, and -499 was increased at 10 min reperfusion with PoCo vs. IFR; however, that of miRNA-1, -24, -208b, and -499 was already increased at 60 min ischemia and probably reflects falsely positive results. Five mRNAs were different with PoCo vs. IFR. In silico analysis identified a tentative connection between three miRNAs and five mRNAs with the biological functions “cell death”, “inflammatory response” and/or “glucose metabolism”. If at all, only miRNA-29b, -133a, and -146b fulfill the minimal temporal requirements for a potential causal involvement in cardioprotection by PoCo.

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Acknowledgments

The authors’ studies were supported by the Dr. Heinz-Horst-Deichmann Foundation. The technical assistances of Sandra Krüger and Jelena Löblein are gratefully acknowledged.

Ethical standards

The experimental protocols were approved by the Bioethical Committee of the district of Düsseldorf (G1240/11).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Institute for Pathophysiology, University of Essen Medical School, Essen, Germany

    Theodor Baars, Andreas Skyschally, Gerd Heusch & Petra Kleinbongard

  2. Institute of Cell Biology, University of Essen Medical School, Essen, Germany

    Ludger Klein-Hitpass

  3. Division of Gastroenterology and Hepatology, University of Essen Medical School, Essen, Germany

    Elke Cario

  4. Clinic of Cardiology, University of Essen Medical School, Essen, Germany

    Theodor Baars & Raimund Erbel

  5. Institut für Pathophysiologie, Universitätsklinikum Essen, Hufelandstr, 55 45122, Essen, Germany

    Petra Kleinbongard

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  1. Theodor Baars
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Correspondence to Petra Kleinbongard.

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Baars, T., Skyschally, A., Klein-Hitpass, L. et al. microRNA expression and its potential role in cardioprotection by ischemic postconditioning in pigs. Pflugers Arch - Eur J Physiol 466, 1953–1961 (2014). https://doi.org/10.1007/s00424-013-1429-3

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