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


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.


CONCLUSIONS
EMPs can promote the activation of GPIIb/IIIa in platelets and platelet aggregation by the PDI which is carried on the surface of EMPs.
The 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.|Department of Radiology Medicine, Qilu Hospital of Shandong University, Ji'nan 250012, P.R. China.
Guan-Qi
GQ
Fan
The 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.|Department of Geriatrics, Qilu Hospital of Shandong University, Ji'nan 250012, P.R.China.
Ran-Ran
RR
Qin
The 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.
Yi-Hui
YH
Li
Department of Emergency, Donggang People's Hospital, Rizhao, 276800, P.R. China.
Dai-Jun
DJ
Song
The 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.
Tong-Shuai
TS
Chen
The 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.
Wei
W
Zhang
The 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.
Ming
M
Zhong
The 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.
Yun
Y
Zhang
The 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.|Department of Geriatrics, Qilu Hospital of Shandong University, Ji'nan 250012, P.R.China.
Yan-Qiu
YQ
Xing
The 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.|Department of Geriatrics, Qilu Hospital of Shandong University, Ji'nan 250012, P.R.China.
Zhi-Hao
ZH
Wang
D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000187:drug effects / Q000201:enzymology*; D002478:Cells, Cultured; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D024821:Metabolic Syndrome / Q000097:blood / Q000201:enzymology*; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D019704:Protein Disulfide-Isomerases / Q000037:antagonists & inhibitors / Q000097:blood*; D015398:Signal Transduction; D013997:Time Factors
D004791:Enzyme Inhibitors; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C546937:SELP protein, human; D019704:Protein Disulfide-Isomerases
endothelial microparticles; insulin resistance; platelet activation; protein disulfide isomerase