Research Paper Volume 13, Issue 14 pp 18718—18739
Endothelial microparticle-associated protein disulfide isomerase increases platelet activation in diabetic coronary heart disease
- 1 The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China
- 2 Department of Geriatric Medicine, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China
- 3 Department of General Practice, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China
- 4 Department of Geriatric Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Shandong key Laboratory of Cardiovascular Proteomics, Jinan 250012, Shandong, China
- 5 Department of Cardiology, The Affiliated Cardiovascular Hospital of Qingdao University, Qingdao 266071, Shandong, China
Received: December 18, 2020 Accepted: June 29, 2021 Published: July 20, 2021
https://doi.org/10.18632/aging.203316How to Cite
Copyright: © 2021 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Endothelial microparticles (EMPs) carrying the protein disulfide isomerase (PDI) might play a key role in promoting platelet activation in diabetes. This study aimed to examine the activation of platelets, the amounts of MPs, PMPs, and EMPs, and the concentration and activity of PDI in patients with diabetic coronary heart disease (CHD) and non-diabetic CHD.
Methods: Patients with CHD (n=223) were divided as non-diabetic CHD (n=121) and diabetic CHD (n=102). Platelet activation biomarkers, circulating microparticles (MPs), the concentration of protein disulfide isomerase (PDI), and MP-PDI activity were determined. The effect of EMPs on platelet activation was investigated in vitro. Allosteric GIIb/IIIa receptors that bind to PDI were detected by a proximity ligation assay (PLA).
Results: Platelet activation, platelet-leukocyte aggregates, circulating MPs, EMPs, PDI, and MP-PDI activity in the diabetic CHD group were significantly higher than in the non-diabetic CHD group (P<0.05). Diabetes (P=0.006) and heart rate <60 bpm (P=0.047) were associated with elevated EMPs. EMPs from diabetes increased CD62p on the surface of the platelets compared with the controls (P<0.01), which could be inhibited by the PDI inhibitor RL90 (P<0.05). PLA detected the allosteric GIIb/IIIa receptors caused by EMP-PDI, which was also inhibited by RL90.
Conclusions: In diabetic patients with CHD, platelet activation was significantly high. Diabetes and heart rate <60 bpm were associated with elevated EMPs and simultaneously increased PDI activity on EMP, activating platelets through the allosteric GPIIb/IIIa receptors.