Oncotarget

Research Papers:

Endothelial cells microparticle-associated protein disulfide isomerase promotes platelet activation in metabolic syndrome

Guan-qi Fan _, Ran-ran Qin, Yi-hui Li, Dai-jun Song, Tong-shuai Chen, Wei Zhang, Ming Zhong, Yun Zhang, Yan-qiu Xing and Zhi-hao Wang

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2016; 7:83231-83240. https://doi.org/10.18632/oncotarget.13081

Metrics: PDF 866 views  |   HTML 993 views  |   ?  


Abstract

Guan-qi Fan1,2,*, Ran-ran Qin1,3,*, Yi-hui Li1, Dai-jun Song4, Tong-shuai Chen1, Wei Zhang1, Ming Zhong1, Yun Zhang1, Yan-qiu Xing1,3, Zhi-hao Wang1,3

1The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology Qilu Hospital of Shandong University, Ji’nan 250012, P.R. China

2Department of Radiology Medicine, Qilu Hospital of Shandong University, Ji’nan 250012, P.R. China

3Department of Geriatrics, Qilu Hospital of Shandong University, Ji’nan 250012, P.R.China

4Department of Emergency, Donggang People’s Hospital, Rizhao, 276800, P.R. China

*These authors have contributed equally to this work

Correspondence to:

Zhi-hao Wang, email: wangzhihaosdu@126.com

Keywords: protein disulfide isomerase, platelet activation, insulin resistance, endothelial microparticles

Received: May 02, 2016    Accepted: October 17, 2016    Published: November 04, 2016

ABSTRACT

Background: Metabolic syndrome (MetS) is a common challenge in the world, and the platelet activation is enhanced in MetS patients. However, the fundamental mechanism that underlies platelet activation in MetS remains incompletely understood. Endothelial cells are damaged seriously in MetS patients, then they release more endothelial microparticles (EMPs). After all, whether the EMPs participate in platelet activation is still obscure. If they were, how did they work?

Results: We demonstrated that the levels of EMPs, PMPs (platelet derived microparticles) and microparticle-carried-PDI activity increased in MetS patients. IR endothelial cells released more EMPs, the EMP-PDI was more activated. EMPs can enhance the activation of CD62P, GPIIb/IIIa and platelet aggregation and this process can be partly inhibited by PDI inhibitor such as RL90 and rutin. Activated platelets stimulated by EMPs expressed more PDI on cytoplasm and released more PMPs.

Materials and Methods: We obtained plasma from 23 MetS patients and 8 normal healthy controls. First we built insulin resistance (IR) model of human umbilical vein endothelial cells (HUVECs), and then we separated EMPs from HUVECs culture medium and used these EMPs to stimulate platelets. Levels of microparticles, P-selectin(CD62P), Glycoprotein IIb/IIIa (GPIIb/IIIa) were detected by flow cytometry and levels of EMPs were detected by enzyme-linked immunosorbent assay (ELISA). The protein disulfide isomerase (PDI) activity was detected by insulin transhydrogenase assay. Platelet aggregation was assessed by turbidimetry.

Conclusion: EMPs can promote the activation of GPIIb/IIIa in platelets and platelet aggregation by the PDI which is carried on the surface of EMPs.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 13081