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

Pilz, Patrick M.; Hamza, Ouafa; Gidlöf, Olof LU ; Gonçalves, Ines F.; Tretter, Eva Verena; Trojanek, Sandra; Abraham, Dietmar; Heber, Stefan; Haller, Paul M. and Podesser, Bruno K., et al. (2019) In International Journal of Cardiology 285. p.72-79
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... (More)

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.

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published
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keywords
Epigenetic, ErbB receptors, Inflammation, Myocardial infarction, Neuregulin-1, Remote ischemic perconditioning
in
International Journal of Cardiology
volume
285
pages
72 - 79
publisher
Elsevier
external identifiers
  • scopus:85063079222
ISSN
0167-5273
DOI
10.1016/j.ijcard.2019.03.003
language
English
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yes
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1d3e0dd0-13be-4c82-a262-d2c9c4b0ccb7
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2019-03-29 14:15:38
date last changed
2019-10-15 07:01:03
@article{1d3e0dd0-13be-4c82-a262-d2c9c4b0ccb7,
  abstract     = {<p>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.</p>},
  author       = {Pilz, Patrick M. and Hamza, Ouafa and Gidlöf, Olof and Gonçalves, Ines F. and Tretter, Eva Verena and Trojanek, Sandra and Abraham, Dietmar and Heber, Stefan and Haller, Paul M. and Podesser, Bruno K. and Kiss, Attila},
  issn         = {0167-5273},
  keyword      = {Epigenetic,ErbB receptors,Inflammation,Myocardial infarction,Neuregulin-1,Remote ischemic perconditioning},
  language     = {eng},
  month        = {03},
  pages        = {72--79},
  publisher    = {Elsevier},
  series       = {International Journal of Cardiology},
  title        = {Remote ischemic perconditioning attenuates adverse cardiac remodeling and preserves left ventricular function in a rat model of reperfused myocardial infarction},
  url          = {http://dx.doi.org/10.1016/j.ijcard.2019.03.003},
  volume       = {285},
  year         = {2019},
}