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19.03.2020

Exendin-4 Ameliorates Cardiac Remodeling in Experimentally Induced Myocardial Infarction in Rats by Inhibiting PARP1/NF-κB Axis in A SIRT1-Dependent Mechanism

verfasst von: Refaat A. Eid, Samah A. Alharbi, Attalla Farag El-kott, Samy M. Eleawa, Mohamed Samir Ahmed Zaki, Fahmy El-Sayed, Muhammad Alaa Eldeen, Hussain Aldera, Abd Al-Rahman Salem Al-Shudiefat

Erschienen in: Cardiovascular Toxicology | Ausgabe 4/2020

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Abstract

Sirt1 is a potent inhibitor of both poly(ADP-ribose) polymerases1 (PARP1) and NF-kB. This study investigated the cardioprotective effect of exendin-4 on cardiac function and remodeling in rats after an expreimentally-induced myocardial infarction (MI) and explored if this protection involves SIRT1/PARP1 axis. Rats were divided into five groups (n = 10/each): sham, sham + exendin-4 (25 nmol/kg/day i.p.), MI (induced by LAD occlusion), MI + exendin-4, and sham + exendin-4 + EX527 (5 mg/2×/week) (a SIRT1 inhibitor). All treatments were given for 6 weeks post the induction of MI. In sham-operated and MI-induced rats, exendin-4 significantly upregulated Bcl-2 levels, enhanced activity, mRNA, and levels of SIRT1, inhibited activity, mRNA, and levels of PARP1, and reduced ROS generation and PARP1 acetylation. In MI-treated rats, these effects were associated with improved cardiac architectures and LV function, reduced collagen deposition, and reduced mRNA and total levels of TNF-α and IL-6, as well as, the activation of NF-κB p65. In addition, exendin-4 inhibited the interaction of PARP1 with p300, TGF-β1, Smad3, and NF-κB p65 and signficantly reduced mRNA and protein levels of collagen I/III and protein levels of MMP2/9. In conclusion, exendin-4 is a potent cardioprotective agent that prevents post-MI inflammation and cardiac remodeling by activating SIRT1-induced inhibition of PARP1.

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Titel: Exendin-4 Ameliorates Cardiac Remodeling in Experimentally Induced Myocardial Infarction in Rats by Inhibiting PARP1/NF-κB Axis in A SIRT1-Dependent Mechanism
verfasst von: Refaat A. Eid
Samah A. Alharbi
Attalla Farag El-kott
Samy M. Eleawa
Mohamed Samir Ahmed Zaki
Fahmy El-Sayed
Muhammad Alaa Eldeen
Hussain Aldera
Abd Al-Rahman Salem Al-Shudiefat
Publikationsdatum: 19.03.2020
Verlag: Springer US
Erschienen in: Cardiovascular Toxicology / Ausgabe 4/2020
Print ISSN: 1530-7905
Elektronische ISSN: 1559-0259
DOI: https://doi.org/10.1007/s12012-020-09567-5

Springer Medizin

Abstract

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