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Pflügers Archiv - European Journal of Physiology

, Volume 466, Issue 10, pp 1953–1961 | Cite as

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

  • Theodor Baars
  • Andreas Skyschally
  • Ludger Klein-Hitpass
  • Elke Cario
  • Raimund Erbel
  • Gerd Heusch
  • Petra KleinbongardEmail author
Molecular and cellular mechanisms of disease

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.

Keywords

Cardioprotection Ischemic postconditioning MicroRNA Pigs 

Notes

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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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Theodor Baars
    • 1
    • 4
  • Andreas Skyschally
    • 1
  • Ludger Klein-Hitpass
    • 2
  • Elke Cario
    • 3
  • Raimund Erbel
    • 4
  • Gerd Heusch
    • 1
  • Petra Kleinbongard
    • 1
    • 5
    Email author
  1. 1.Institute for PathophysiologyUniversity of Essen Medical SchoolEssenGermany
  2. 2.Institute of Cell BiologyUniversity of Essen Medical SchoolEssenGermany
  3. 3.Division of Gastroenterology and HepatologyUniversity of Essen Medical SchoolEssenGermany
  4. 4.Clinic of CardiologyUniversity of Essen Medical SchoolEssenGermany
  5. 5.Institut für PathophysiologieUniversitätsklinikum EssenEssenGermany

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