Platelet activation in diabetic mice models: the role of vascular endothelial cell-derived protein disulfide isomerase-mediated GP IIb/IIIa receptor activation.

Ran-Ran Qin,Hui Zhu,Feng Wang,Yan-Qiu Xing,Zhi-Hao Wang,Ming Song,Ming Zhong,Wei Zhang,Pei-Lin Lin

doi:10.18632/aging.102192

Abstract

GP IIb/IIIa receptor activation plays an important role in thrombosis. The mechanism of early activation of GP IIb/IIIa receptors in diabetic conditions remains unknown. The purpose of this study was to investigate the release of Endothelial microparticle (EMP)-associated protein disulfide isomerase (PDI) after endothelial cell injury induced in diabetes and the changes in platelet activation. We produced an animal model of type 2 diabetes mellitus using ApoE−/− mice. Normal ApoE−/− and diabetic mice were allocated to four groups (n = 15): normal diet, normal diet plus rutin, diabetic, and diabetes plus rutin. The EMP-PDI content and GP IIb/IIIa expression of mice platelets were determined. In addition, EMPs obtained from the four groups were pretreated with the PDI inhibitor rutin; then, their effects on the platelets of normal C57 mice were characterized. Compared with the normal diet group, the diabetic group had significantly increased plasma EMP-PDI content and accelerated platelet activation by increased GP IIb/IIIa expression. In conclusion, EMP-PDI promotes early platelet activation through glycoprotein (GP) IIb/IIIa receptors present on platelet surface in the diabetic state. However, this process could be partially suppressed by the administration of rutin.

Highlights

The prevalence of type 2 diabetes mellitus is rapidly increasing, and it has emerged as a major public health problem worldwide
The purpose of this study was to investigate the release of Endothelial microparticle (EMP)-associated protein disulfide isomerase (PDI) after endothelial cell injury induced in diabetes and the changes in platelet activation
There was no significant difference among mice of different ages in the normal diet group (P < 0.05, Figure 1B); At week 10, the intraperitoneal glucose tolerance test (IPGTT) result in mice with diabetes was higher than that reported at week 4 in mice with diabetes and mice receiving a normal diet

Summary

Introduction

The prevalence of type 2 diabetes mellitus is rapidly increasing, and it has emerged as a major public health problem worldwide. One of the most important complications of diabetes mellitus is cardiovascular disease [1,2,3]. Because most acute cardiovascular events are associated with thrombosis, intensive antiplatelet therapy offers a major clinical benefit to diabetic patients. Diabetic patients have significantly higher platelet aggregation and activation than nondiabetic patients, including those undergoing dual www.aging-us.com antiplatelet therapy [4,5,6]. This suggests that the mechanism of platelet activation in the diabetic state has not been fully elucidated. The identification of the key molecules that accurately regulate the activation of these receptors may provide a novel approach for antiplatelet therapy

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