Protein kinases are involved in the cardioprotective effects activated by platelet glycoprotein IIb/IIIa inhibitor tirofiban at reperfusion in rats in vivo.

Autor: Chang ST; Division of Cardiology, Chiayi Chang Gung Memorial Hospital, Chai Yi Hsien, Taiwan; Chiayi School, Chang Gung Institute of Technology, Chai Yi Hsien, Taiwan; School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan. Electronic address: cst1234567@yahoo.com.tw., Yang YT; Section of Health Informatics, Institute of Public Health, National Defense Medical Center and University, Taipei, Taiwan., Chu CM; Section of Health Informatics, Institute of Public Health, National Defense Medical Center and University, Taipei, Taiwan., Pan KL; Division of Cardiology, Chiayi Chang Gung Memorial Hospital, Chai Yi Hsien, Taiwan; Chiayi School, Chang Gung Institute of Technology, Chai Yi Hsien, Taiwan; School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan., Hsu JT; Division of Cardiology, Chiayi Chang Gung Memorial Hospital, Chai Yi Hsien, Taiwan; Chiayi School, Chang Gung Institute of Technology, Chai Yi Hsien, Taiwan; School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan., Hsiao JF; Division of Cardiology, Chiayi Chang Gung Memorial Hospital, Chai Yi Hsien, Taiwan; Chiayi School, Chang Gung Institute of Technology, Chai Yi Hsien, Taiwan; School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan., Lin YS; Division of Cardiology, Chiayi Chang Gung Memorial Hospital, Chai Yi Hsien, Taiwan; Chiayi School, Chang Gung Institute of Technology, Chai Yi Hsien, Taiwan; School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan., Chung CM; Division of Cardiology, Chiayi Chang Gung Memorial Hospital, Chai Yi Hsien, Taiwan; Chiayi School, Chang Gung Institute of Technology, Chai Yi Hsien, Taiwan; School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2018 Aug 05; Vol. 832, pp. 33-38. Date of Electronic Publication: 2018 May 17.
DOI: 10.1016/j.ejphar.2018.05.014
Abstrakt: The thrombolytic effect of platelet glycoprotein IIb/IIIa inhibitors (GP IIb/IIIa inhibitors) in myocardial infarction has been well established. Nevertheless, data on the mechanism of the cardioprotective effect of GP IIb/IIIa inhibitors in ischemic-reperfusion injury (IR) are lacking. Sprague-Dawley rats received 120 min of coronary ischemia and 180 min of reperfusion. A GP IIb/IIIa inhibitor was given via continuous intravenous infusion at a rate of 2 μg/kg/min 30 min prior to reperfusion with/without inhibitors of PKCε (chelerythrine), PI3 kinase and Akt (wortmannin), p38 MAPK (SB203582), p42/44 MAPK (PD98059) and ERK1/2 (u0126) 15 min prior to the GP IIb/IIIa inhibitor. Protein isolation and analysis were performed by Western blot analysis. The cardioprotective effects were measured as the ratio of myocardial necrotic area to the area at risk (AAR) and the apoptotic index (AI) calculated as the percentage of myocytes positive for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling of all myocytes stained by 4', 6-diamidino-2-phenylindole. The GP IIb/IIIa inhibitor reduced the ratio of myocardial necrotic area to AAR and AI, and also exerted an immediate cardioprotective effect by activating multiple signaling pathways including phosphorylation and activation of PKCε, PI3 kinase, Akt, p38 MAPK, p42/44 MAPK and ERK1/2. However, there were no significant increases in the phosphorylation of Raf and MEK1/2. We concluded that the GP IIb/IIIa inhibitor reduced the extent of cardiac IR and significantly ameliorate the apoptosis of myocytes in the rats. In addition, the cardioprotective effect was mediated through the activation of multiple signal transduction pathways.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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