Surface expression of collagen receptor Fc receptor-gamma/glycoprotein VI is enhanced on platelets in type 2 diabetes and mediates release of CD40 ligand and activation of endothelial cells.
Diabetes is associated with an enhanced collagen-mediated platelet activation that contributes significantly to thromboischemic complications. In this study, the platelet collagen receptor glycoprotein VI (GPVI) was studied in 385 patients with type 2 diabetes. Surface expression of the platelet Fc receptor that forms a functional complex with GPVI was significantly increased in patients with diabetes compared with those without diabetes (P = 0.02). Fc receptor expression correlated with GPVI expression and was found to be independently associated with diabetes (r = 0.529, P < 0.001). Stimulation of GPVI through a specific anti-GPVI monoclonal antibody significantly enhanced surface expression of CD40L (P = 0.006). Because CD40L is a potent platelet-derived cytokine that is involved in thrombosis and atherosclerosis, we evaluated the effect of GPVI-mediated release of CD40L on activation of endothelial cells. Coincubation of GPVI-stimulated platelets resulted in substantial enhanced endothelial surface expression of CD62P, alphavbeta3, and intercellular adhesion molecule 1 (P < 0.05) and secretion of monocyte chemoattractant protein 1 of cultured human umbilical vein endothelial cells (P < 0.01). These results suggest that the function of collagen receptor GPVI is altered in type 2 diabetes and may play an important role in atherothrombotic complications. Inhibition of GPVI may be a promising pharmacological target in the treatment of high-risk diabetic patients.
Cabeza
Natalia
N
Medizinische Klinik, Klinikum rechts der IsarDeutsches Herzzentrum, Technische Universität München, München, Germany.
Li
Zhongyan
Z
Schulz
Christian
C
Kremmer
Elisabeth
E
Massberg
Steffen
S
Bültmann
Andreas
A
Gawaz
Meinrad
M
D001792:Blood Platelets / Q000276:immunology / Q000502:physiology*; D023201:CD40 Ligand / Q000097:blood*; D015815:Cell Adhesion Molecules / Q000502:physiology; D002460:Cell Line; D018932:Chemokine CCL2 / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology / Q000502:physiology / Q000503:physiopathology*; D005434:Flow Cytometry; D006801:Humans; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D038981:Receptors, Collagen / Q000097:blood*; D017452:Receptors, IgG / Q000502:physiology*; D014471:Umbilical Veins
D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D010980:Platelet Membrane Glycoproteins; D038981:Receptors, Collagen; D017452:Receptors, IgG; C098341:platelet membrane glycoprotein VI; D023201:CD40 Ligand