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Exendin-4 Ameliorates Cardiac Remodeling in Experimentally Induced Myocardial Infarction in Rats by Inhibiting PARP1/NF-κB Axis in A SIRT1-Dependent Mechanism.
Eid, Refaat A; Alharbi, Samah A; El-Kott, Attalla Farag; Eleawa, Samy M; Zaki, Mohamed Samir Ahmed; El-Sayed, Fahmy; Eldeen, Muhammad Alaa; Aldera, Hussain; Al-Shudiefat, Abd Al-Rahman Salem.
Afiliación
  • Eid RA; Department of Pathology, College of Medicine, King Khalid University, Abha, Saudi Arabia. refaat_eid@yahoo.com.
  • Alharbi SA; Department of Physiology, College of Medicine, Umm Al-Qura University, Mekkah, Saudi Arabia.
  • El-Kott AF; Department of Biology, College of Science, King Khalid University, P.O. 641, Abha, 61421, Saudi Arabia.
  • Eleawa SM; Department of Zoology, Faculty of Science, Damanhour University, Damanhour, Egypt.
  • Zaki MSA; Department of Applied Medical Sciences, College of Health Sciences, PAAET, Shuwaikh, Kuwait.
  • El-Sayed F; Department of Anatomy, College of Medicine, King Khalid University, P.O. 641, Abha, 61421, Saudi Arabia.
  • Eldeen MA; Department of Histology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
  • Aldera H; Department of Pathology, College of Medicine, King Khalid University, Abha, Saudi Arabia.
  • Al-Shudiefat AAS; Biology Department, Physiology Section, Faculty of Science, Zagazig University, Zagazig, Egypt.
Cardiovasc Toxicol ; 20(4): 401-418, 2020 08.
Article en En | MEDLINE | ID: mdl-32193876
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-ß1, 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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: FN-kappa B / Función Ventricular Izquierda / Remodelación Ventricular / Miocitos Cardíacos / Incretinas / Sirtuina 1 / Poli(ADP-Ribosa) Polimerasa-1 / Exenatida / Antiinflamatorios / Infarto del Miocardio Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cardiovasc Toxicol Asunto de la revista: ANGIOLOGIA / CARDIOLOGIA / TOXICOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Arabia Saudita Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: FN-kappa B / Función Ventricular Izquierda / Remodelación Ventricular / Miocitos Cardíacos / Incretinas / Sirtuina 1 / Poli(ADP-Ribosa) Polimerasa-1 / Exenatida / Antiinflamatorios / Infarto del Miocardio Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cardiovasc Toxicol Asunto de la revista: ANGIOLOGIA / CARDIOLOGIA / TOXICOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Arabia Saudita Pais de publicación: Estados Unidos