Elevated release of sCD40L from platelets of diabetic patients by thrombin, glucose and advanced glycation end

Nerea Varo1, Peter Libby, Rebecca Nuzzo

  • 1Donald W Reynolds Cardiovascular Clinical Research Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Insights

Diabetic patients show increased CD40 ligand (CD40L) within platelets and greater release when stimulated. Glucose and advanced glycation end products (AGEs) may trigger this, explaining higher soluble CD40L (sCD40L) in diabetes.

Area of Science:

  • Cardiovascular Biology
  • Immunology
  • Metabolic Disease Research

Background:

  • The CD40/CD40L pathway is implicated in atherosclerosis.
  • Elevated soluble CD40L (sCD40L) levels are observed in diabetic patients and predict cardiovascular events.

Purpose of the Study:

  • To compare CD40/CD40L surface expression on platelets and T lymphocytes in diabetic and control subjects.
  • To investigate if glucose and advanced glycation end products (AGEs) stimulate sCD40L release.

Main Methods:

  • Compared surface CD40/CD40L expression on platelets and T lymphocytes.
  • Assessed intracellular CD40L content in platelets.
  • Measured sCD40L release from platelets stimulated by thrombin.
  • Investigated the effect of glucose and AGEs on platelet sCD40L release and megakaryocyte CD40L expression.

Main Results:

  • No differences in constitutive or inducible surface CD40/CD40L expression on platelets or T lymphocytes between groups.
  • Diabetic patients had higher intracellular platelet CD40L.
  • Thrombin-stimulated sCD40L release from platelets was significantly greater in diabetic patients.
  • Glucose and AGEs induced sCD40L release and CD40L expression in vitro.

Conclusions:

  • Diabetic patients exhibit increased intracellular CD40L in platelets and enhanced inducible sCD40L release.
  • Glucose and AGEs are identified as potential triggers for elevated sCD40L in diabetic patients.

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