Remote ischemic perconditioning attenuates adverse cardiac remodeling and preserves left ventricular function in a rat model of reperfused myocardial infarction

Research output: Contribution to journalArticle

Abstract

Aims: Remote ischemic conditioning (RIC) is considered a potential clinical approach to reduce myocardial infarct size and ameliorate adverse post-infarct left ventricular (LV) remodeling, however the mechanisms are unknown. The aim was to clarify the impact of RIC on Neuregulin-1 (NRG-1)/ErbBs expression, inflammation and LV hemodynamic function. Methods and results: Male Sprague-Dawley rats were subjected to 30 min occlusion of the left coronary artery (LCA) followed by 2 weeks of reperfusion and separated into three groups: (1) sham operated (without LCA occlusion); (2) Myocardial ischemia/reperfusion (MIR) and (3) remote ischemic perconditioning group (MIR + RIPerc). Cardiac structural and functional changes were evaluated by echocardiography and on the isolated working heart system. The level of H3K4me3 at the NRG-1 promoter, and both plasma and LV tissue levels of NRG-1 were assessed. The expression of pro-inflammatory cytokines, ECM components and ErbB receptors were assessed by RT-qPCR. MIR resulted in a significant decrease in LV function and enlargement of LV chamber. This was accompanied with a decrease in the level of H3K4me3 at the NRG-1 promoter. Consequently NRG-1 protein levels were reduced in the infarcted myocardium. Subsequently, an upregulated influx of CD68+ macrophages, high expression of MMP-2 and -9 as well as an increase of IL-1β TLR-4, TNF-α TNC expression were observed. In contrast, RIPerc significantly decreased inflammation and improved LV function in association with the enhancement of NRG-1 levels and ErbB3 expression. Conclusions: These findings may reveal a novel anti-remodeling and anti-inflammatory effect of RIPerc, involving activation of NRG-1/ErbB3 signaling.

Details

Authors
  • Patrick M. Pilz
  • Ouafa Hamza
  • Olof Gidlöf
  • Ines F. Gonçalves
  • Eva Verena Tretter
  • Sandra Trojanek
  • Dietmar Abraham
  • Stefan Heber
  • Paul M. Haller
  • Bruno K. Podesser
  • Attila Kiss
Organisations
External organisations
  • Medical University of Vienna
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cardiac and Cardiovascular Systems

Keywords

  • Epigenetic, ErbB receptors, Inflammation, Myocardial infarction, Neuregulin-1, Remote ischemic perconditioning
Original languageEnglish
JournalInternational Journal of Cardiology
Publication statusE-pub ahead of print - 2019 Mar 6
Publication categoryResearch
Peer-reviewedYes