Phosphoryaltion levels of ERK5 in acute myocardial infarction patients and its role in platelet activation in vitro
10.3969/j.issn.1672-8467.2017.04.008
- VernacularTitle:ERK5在急性心肌梗死患者中的磷酸化水平及对体外血小板激活的影响
- Author:
Wen GAO
;
Jian LI
;
Huanchun NI
;
Kun XIE
;
Xinping LUO
- Keywords:
ERK5;
platelet;
thrombosis;
acute myocardial infarction
- From:
Fudan University Journal of Medical Sciences
2017;44(4):441-446
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the phosphorylation levels of extracellular signal-regulated kinase 5 (ERK5) in acute myocardial infarction (AMI) patients and the effects of ERK5 selective inhibitor XMD8-92 on human platelet activation in vitro,and to explore its mechanism.Methods Western blot was applied to detect the phosphorylation levels of ERK5,Akt473 and Akt308 in AMI patients (n =34) and stable angina patients (n =33,control).The effects of different concentration of XMD8-92 on human platelet aggregation induced by collagen was tested by aggregometer in vitro.The release of ATP was measured simultaneously by luciferase detection.The effects of XMD8-92 on integrin aIIbβ3 were detected by platelet spreading on immobilized fibrinogen and clot retraction.The effects of XMD8-92 on phosphorylation levels of Akt473,Akt308 PTEN370 and ERK5 were detected by Western blot.Results The levels of phosphor-Akt473,Akt308 and phosphor-ERK5 were significantly higher in AMI patients than that in control group (P＜0.05).ERK5 inhibitor XMD8-92 diminished collagen-induced platelet aggregation,ATP secretion,the average area of platelet spreading on immobilized fibrinogen and the clot retraction extent.The levels of phosphor-Akt (Ser-473/Thr-308) and phosphor-PTEN (Ser370) were significantly down-regulated in the presence of XMD8-92.Conclusions ERK5 plays a role in platelet activation in AMI process.It regulates platelet activation by regulating PTEN and Akt phosphorylation.Its specific inhibitor is hoped to be new antithrombotic drug.
