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01-03-2018 | Original Contribution

Cardioprotective effect of ghrelin against myocardial infarction-induced left ventricular injury via inhibition of SOCS3 and activation of JAK2/STAT3 signaling

Authors: Refaat A. Eid, Mahmoud A. Alkhateeb, Samy Eleawa, Fahaid H. Al-Hashem, Mubarak Al-Shraim, Attalla Farag El-kott, Mohamed Samir Ahmed Zaki, Mohammad A. Dallak, Hussain Aldera

Published in: Basic Research in Cardiology | Issue 2/2018

Abstract

The molecular mechanisms through which ghrelin exerts its cardioprotective effects during cardiac remodeling post-myocardial infarction (MI) are poorly understood. The aim of this study was to investigate whether the cardioprotection mechanisms are mediated by modulation of JAK/STAT signaling and what triggers this modulation. Rats were divided into six groups (n = 12/group): control, sham, sham + ghrelin (100 µg/kg, s.c., daily, starting 1 day post-MI), MI, MI+ ghrelin, and MI+ ghrelin+ AG490, a potent JAK2 inhibitor (5 mg/kg, i.p., daily). All treatments were administered for 3 weeks. Administration of ghrelin to MI rats improved left ventricle (LV) architecture and restored cardiac contraction. In remote non-infarcted areas of MI rats, ghrelin reduced cardiac inflammation and lipid peroxidation and enhanced antioxidant enzymatic activity. In addition, independent of the growth factor/insulin growth factor-1 (GF/IGF-1) axis, ghrelin significantly increased the phosphorylation of JAK2 and Tyr702 and Ser727 residues of STAT3 and inhibited the phosphorylation of JAK1 and Tyr701 and Ser727 residues of STAT1, simultaneously increasing the expression of BCL-2 and decreasing in the expression of BAX, cleaved CASP3, and FAS. This effect coincided with decreased expression of SOCS3. All these beneficial effects of ghrelin, except its inhibitory action on IL-6 expression, were partially and significantly abolished by the co-administration of AG490. In conclusion, the cardioprotective effect of ghrelin against MI-induced LV injury is exerted via activation of JAK2/STAT3 signaling and inhibition of STAT1 signaling. These effects were independent of the GF/IGF-1 axis and could be partially mediated via inhibition of cardiac IL-6.

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Title: Cardioprotective effect of ghrelin against myocardial infarction-induced left ventricular injury via inhibition of SOCS3 and activation of JAK2/STAT3 signaling
Authors: Refaat A. Eid
Mahmoud A. Alkhateeb
Samy Eleawa
Fahaid H. Al-Hashem
Mubarak Al-Shraim
Attalla Farag El-kott
Mohamed Samir Ahmed Zaki
Mohammad A. Dallak
Hussain Aldera
Publication date: 01-03-2018
Publisher: Springer Berlin Heidelberg
Published in: Basic Research in Cardiology / Issue 2/2018
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-018-0671-4

2024 ASCO Annual Meeting

Springer Medicine

Cardioprotective effect of ghrelin against myocardial infarction-induced left ventricular injury via inhibition of SOCS3 and activation of JAK2/STAT3 signaling

Abstract

2024 ASCO Annual Meeting

Springer Medicine

Abstract

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