Diabetes and Hyperglycemia Affect Platelet GPIIIa Expression: Effects on Adhesion Potential of Blood Platelets from Diabetic Patients under In Vitro Flow Conditions
Open Access
- 2 May 2020
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 21 (9), 3222
- https://doi.org/10.3390/ijms21093222
Abstract
Blood platelets play a crucial role in the early stages of atherosclerosis development. The process is believed to require firm adhesion of platelets to atherosclerosis-prone sites of the artery. However, little evidence exists regarding whether the blood platelets of individuals with pathological conditions associated with atherosclerosis have higher potential for adhesion. This process is to a large extent dependent on receptors present on the platelet membrane. Therefore, the aim of the presented study was to determine whether blood platelets from diabetic patients have higher capacity of adhesion under flow conditions and how diabetes affects one of the crucial platelet receptors involved in the process of adhesion—GPIIIa. The study compares the ability of platelets from non-diabetic and diabetic humans to interact with fibrinogen and von Willebrand factor, two proteins found in abundance on an inflamed endothelium, under flow conditions. The activation and reactivity of the blood platelets were also characterized by flow cytometry. Platelets from diabetic patients did not demonstrate enhanced adhesion to either studied protein, although they presented increased basal activation and responsiveness towards low concentrations of agonists. Platelets from diabetic patients were characterized by lower expression of GPIIIa, most likely due to an enhanced formation of platelet-derived microparticles PMPs, as supported by the observation of elevated concentration of this integrin and of GPIIIa-positive PMPs in plasma. We conclude that altered functionality of blood platelets in diabetes does not increase their adhesive potential. Increased glycation and decrease in the amount of GPIIIa on platelets may be partially responsible for this effect. Therefore, higher frequency of interactions of platelets with the endothelium, which is observed in animal models of diabetes, is caused by other factors. A primary cause may be a dysfunctional vascular wall.Keywords
Funding Information
- Narodowe Centrum Nauki (MAESTRO (No. UMO-2012/06/A/N25/00069))
This publication has 47 references indexed in Scilit:
- Platelet Adhesion from Shear Blood Flow Is Controlled by Near-Wall Rebounding Collisions with ErythrocytesBiophysical Journal, 2011
- Megakaryocyte-derived microparticles: direct visualization and distinction from platelet-derived microparticlesBlood, 2009
- Platelet MicroparticlesArteriosclerosis, Thrombosis, and Vascular Biology, 2005
- Platelet activation in type 2 diabetes mellitusJournal of Thrombosis and Haemostasis, 2004
- Involvement of the beta3 E749ATSTFTN756 region in stabilizing integrin alphaIIbbeta3-ligand interactionJournal of Thrombosis and Haemostasis, 2003
- Mapping the binding domains of the αIIb subunitEuropean Journal of Biochemistry, 2003
- A Critical Role of Platelet Adhesion in the Initiation of Atherosclerotic Lesion FormationThe Journal of Experimental Medicine, 2002
- Does reduced membrane lipid fluidity underlie the altered thrombin-induced expression of integrin αIIbβ3and PADGEM-140 in membranes of platelets from diabetic juveniles?Platelets, 1996
- The Relationship of Chemical Modification of Membrane Proteins and Plasma Lipoproteins to Reduced Membrane Fluidity of Erythrocytes from Diabetic Subjectscclm, 1992
- Evidence for abnormal platelet glycoprotein expression in diabetes mellitusEuropean Journal of Clinical Investigation, 1990