Surface Expression of Collagen Receptor Fc Receptor-γ/Glycoprotein VI Is Enhanced on Platelets in Type 2 Diabetes and Mediates Release of CD40 Ligand and Activation of Endothelial Cells

  1. Natalia Cabeza1,
  2. Zhongyan Li1,
  3. Christian Schulz1,
  4. Elisabeth Kremmer2,
  5. Steffen Massberg1,
  6. Andreas Bültmann1 and
  7. Meinrad Gawaz1
  1. 1Medizinische Klinik Klinikum rechts der Isar and Deutsches Herzzentrum, Technische Universität München, München, Germany
  2. 2Institute of Molecular Immunology, GSF-National Research Center for Environment and Health, München, Germany
  1. Address correspondence and reprint requests to Meinrad Gawaz, MD, Medizinische Klinik, Klinikum rechts der IsarDeutsches Herzzentrum, Technische Universität München, Ismaningerstraße 22, 81675 München, Germany. E-mail: meinrad.gawaz{at}med1.med.tu-muenchen.de

Abstract

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, αvβ3, 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.

Footnotes

  • N.C. and Z.L. contributed equally to this work.

    • Accepted April 19, 2004.
    • Received August 11, 2004.
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