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Diabetes and Vascular Disease Research
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Elevated release of sCD40L from platelets of diabetic patients by thrombin, glucose and advanced glycation end products

Nerea Varo

Area of Cardiovascular Pathophysiology, Center for Applied Medical Research, University of Navarra School of Medicine, Pamplona, Spain

Peter Libby

Donald W. Reynolds Cardiovascular Clinical Research Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, US

Rebecca Nuzzo

Donald W. Reynolds Cardiovascular Clinical Research Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, US

Joseph Italiano

Division of Hematology, Brigham and Women's Hospital, Boston, US

Alessandro Doria

Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston, US

Uwe Schönbeck

Cardiovascular Disease, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Room 7542, Ridgefield, CT 10877, US

The pro-inflammatory CD40/CD40L dyad participates in atherogenesis. Plasma levels of the soluble ligand (sCD40L) predict cardiovascular events and are elevated in diabetic patients. This study compared CD40/CD40L surface expression on platelets and T lymphocytes of diabetic and control subjects, and tested whether glucose and advanced glycation end products (AGEs) stimulate sCD40L release.

Constitutive and inducible surface expression of CD40/CD40L on platelets or T lymphocytes did not differ between diabetic patients (n=9) and controls (n=13). Platelets from diabetic patients contained higher intracellular CD40L than controls (p<0.05) and thrombin stimulated greater platelet sCD40L release in diabetic patients (15.11 ± 16.77 ng/ml) compared to controls (3.64 ± 2.03 ng/ml; p<0.05). Glucose and AGEs induced platelet sCD40L release and CD40L expression in mouse megakaryocytes.

This study demonstrates elevated CD40L content and inducible release from platelets of diabetic patients, and identifies glucose and AGEs as potential triggers of expression and release accounting for the elevated sCD40L plasma levels in these patients.

Key Words: CD40 ligand • inflammation • diabetes • platelets

Diabetes and Vascular Disease Research, Vol. 2, No. 2, 81-87 (2005)
DOI: 10.3132/dvdr.2005.014
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 J Am Coll CardiolHome page
C. Antoniades, C. Bakogiannis, D. Tousoulis, A. S. Antonopoulos, and C. Stefanadis
The CD40/CD40 ligand system: linking inflammation with atherothrombosis.
J. Am. Coll. Cardiol., August 18, 2009; 54(8): 669 - 677.
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