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

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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; Gonçalves, Ines F.; Tretter, Eva Verena; Trojanek, Sandra; Abraham, Dietmar; Heber, Stefan; Haller, Paul M.; Podesser, Bruno K.; Kiss, Attila.

I: International Journal of Cardiology, Vol. 285, 2019, s. 72-79.

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Pilz, Patrick M. ; Hamza, Ouafa ; Gidlöf, Olof ; Gonçalves, Ines F. ; Tretter, Eva Verena ; Trojanek, Sandra ; Abraham, Dietmar ; Heber, Stefan ; Haller, Paul M. ; Podesser, Bruno K. ; Kiss, Attila. / Remote ischemic perconditioning attenuates adverse cardiac remodeling and preserves left ventricular function in a rat model of reperfused myocardial infarction. I: International Journal of Cardiology. 2019 ; Vol. 285. s. 72-79.

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TY - JOUR

T1 - Remote ischemic perconditioning attenuates adverse cardiac remodeling and preserves left ventricular function in a rat model of reperfused myocardial infarction

AU - Pilz, Patrick M.

AU - Hamza, Ouafa

AU - Gidlöf, Olof

AU - Gonçalves, Ines F.

AU - Tretter, Eva Verena

AU - Trojanek, Sandra

AU - Abraham, Dietmar

AU - Heber, Stefan

AU - Haller, Paul M.

AU - Podesser, Bruno K.

AU - Kiss, Attila

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - Epigenetic

KW - ErbB receptors

KW - Inflammation

KW - Myocardial infarction

KW - Neuregulin-1

KW - Remote ischemic perconditioning

U2 - 10.1016/j.ijcard.2019.03.003

DO - 10.1016/j.ijcard.2019.03.003

M3 - Article

C2 - 30904281

AN - SCOPUS:85063079222

VL - 285

SP - 72

EP - 79

JO - International Journal of Cardiology

JF - International Journal of Cardiology

SN - 0167-5273

ER -