Transcriptional Alterations by Ischaemic Postconditioning in a Pig Infarction Model: Impact on Microvascular Protection

Dominika Lukovic, Alfred Gugerell, Katrin Zlabinger, Johannes Winkler, Noemi Pavo, Tamás Baranyai, Z. Giricz, Zoltán V. Varga, Martin Riesenhuber, Andreas Spannbauer, Denise Traxler, András Jakab, Rita Garamvölgyi, Örs Petnehazy, Dietmar Pils, Levente Tóth, Rainer Schulz, Péter Ferdinandy, Mariann Gyöngyösi

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Abstract

Although the application of cardioprotective ischaemia/reperfusion (I/R) stimuli after myocardial infarction (MI) is a promising concept for salvaging the myocardium, translation to a clinical scenario has not fulfilled expectations. We have previously shown that in pigs, ischaemic postconditioning (IPostC) reduces myocardial oedema and microvascular obstruction (MVO), without influencing myocardial infarct size. In the present study, we analyzed the mechanisms underlying the IPostC-induced microvascular protection by transcriptomic analysis, followed by pathway analysis. Closed-chest reperfused MI was induced by 90 min percutaneous balloon occlusion of the left anterior descending coronary artery, followed by balloon deflation in anaesthetised pigs. Animals were randomised to IPostC (n = 8), MI (non-conditioned, n = 8), or Control (sham-operated, n = 4) groups. After three hours or three days follow-up, myocardial tissue samples were harvested and subjected to RNA-seq analysis. Although the transcriptome analysis revealed similar expression between IPostC and MI in transcripts involved in cardioprotective pathways, we identified gene expression changes responding to IPostC at the three days follow-up. Focal adhesion signaling, downregulated genes participating in cardiomyopathy and activation of blood cells may have critical consequences for microvascular protection. Specific analyses of the gene subsets enriched in the endothelium of the infarcted area, revealed strong deregulation of transcriptional functional clusters, DNA processing, replication and repair, cell proliferation, and focal adhesion, suggesting sustentative function in the endothelial cell layer protection and integrity. The spatial and time-dependent transcriptome analysis of porcine myocardium supports a protective effect of IPostC on coronary microvasculature post-MI.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume20
Issue number2
DOIs
Publication statusPublished - Jan 15 2019

Fingerprint

Ischemic Postconditioning
infarction
myocardial infarction
swine
Balloons
Infarction
Swine
Adhesion
Genes
Myocardial Infarction
Salvaging
Deregulation
Endothelial cells
Cell proliferation
myocardium
RNA
Gene expression
balloons
Animals
Focal Adhesions

Keywords

  • acute myocardial infarction
  • ischemia-reperfusion injury
  • ischemic postconditioning
  • porcine model
  • transcriptome

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Transcriptional Alterations by Ischaemic Postconditioning in a Pig Infarction Model : Impact on Microvascular Protection. / Lukovic, Dominika; Gugerell, Alfred; Zlabinger, Katrin; Winkler, Johannes; Pavo, Noemi; Baranyai, Tamás; Giricz, Z.; Varga, Zoltán V.; Riesenhuber, Martin; Spannbauer, Andreas; Traxler, Denise; Jakab, András; Garamvölgyi, Rita; Petnehazy, Örs; Pils, Dietmar; Tóth, Levente; Schulz, Rainer; Ferdinandy, Péter; Gyöngyösi, Mariann.

In: International Journal of Molecular Sciences, Vol. 20, No. 2, 15.01.2019.

Research output: Contribution to journalArticle

Lukovic, D, Gugerell, A, Zlabinger, K, Winkler, J, Pavo, N, Baranyai, T, Giricz, Z, Varga, ZV, Riesenhuber, M, Spannbauer, A, Traxler, D, Jakab, A, Garamvölgyi, R, Petnehazy, Ö, Pils, D, Tóth, L, Schulz, R, Ferdinandy, P & Gyöngyösi, M 2019, 'Transcriptional Alterations by Ischaemic Postconditioning in a Pig Infarction Model: Impact on Microvascular Protection', International Journal of Molecular Sciences, vol. 20, no. 2. https://doi.org/10.3390/ijms20020344
Lukovic, Dominika ; Gugerell, Alfred ; Zlabinger, Katrin ; Winkler, Johannes ; Pavo, Noemi ; Baranyai, Tamás ; Giricz, Z. ; Varga, Zoltán V. ; Riesenhuber, Martin ; Spannbauer, Andreas ; Traxler, Denise ; Jakab, András ; Garamvölgyi, Rita ; Petnehazy, Örs ; Pils, Dietmar ; Tóth, Levente ; Schulz, Rainer ; Ferdinandy, Péter ; Gyöngyösi, Mariann. / Transcriptional Alterations by Ischaemic Postconditioning in a Pig Infarction Model : Impact on Microvascular Protection. In: International Journal of Molecular Sciences. 2019 ; Vol. 20, No. 2.
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