Modulators of intraplatelet calcium concentration affect the binding of thrombospondin to blood platelets in healthy donors and patients with type 2 diabetes mellitus

Eur J Haematol. 2001 Jun;66(6):396-403. doi: 10.1034/j.1600-0609.2001.066006396.x.


Thrombospondin (TSP), which is secreted from alpha-granules of activated platelets, binds to its surface receptor (CD36) in the presence of Ca2+.

Objectives: We monitored how the modulation of intraplatelet Ca2+ affects TSP binding to CD36 on platelets from healthy donors and patients with type 2 diabetes mellitus. We also aimed to verify whether the impaired Ca2+ mobilisation in diabetes influences TSP binding upon the pharmacological modulation of calcium transport.

Methods: Whole blood cytometry was used to monitor TSP release/binding and CD36 presentation in platelets from 28 type 2 patients and 33 healthy donors.

Results: No significant changes in TSP and CD36 levels were revealed between the groups in circulating platelets and TRAP-, collagen- or thrombin-activated platelets. In healthy donors, 1 microM thapsigargin (TG) elevated the TRAP-activated TSP binding (by up to 50%, p<0.001), 5 mM EGTA reversed the effect (by up to 85%, p<0.001), and overcame the effect of TG when used together. Less profoundly expressed effects occurred in the NIDDM group. In both groups TG increased the presentation of CD36 in TRAP-stimulated platelets (p<0.05), whereas EGTA lowered the TRAP-stimulated increase in CD36 (p<0.001). The inhibition of CD36 by EGTA was stronger in healthy volunteers (41% vs. 32%, respectively, p<0.05), whereas the activation by TG was higher in the NIDDM group (11% vs. 27%, p<0.05). When acting together the suppressive effects of EGTA on TG-dependent Ca2+ mobilisation were much attenuated in diabetic subjects (p<0.05).

Conclusion: Both the release of TSP and CD36 presentation are under the influence of agents modulating intracellular Ca2+. Diabetic platelets seem more vulnerable to the releasers of cytosolic [Ca2+] and more resistant to the blockers of cytosolic [Ca2+] mobilisation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism*
  • CD36 Antigens / drug effects
  • CD36 Antigens / metabolism
  • Calcium / metabolism*
  • Diabetes Mellitus, Type 2 / blood*
  • Female
  • Humans
  • Male
  • Matched-Pair Analysis
  • Middle Aged
  • P-Selectin / metabolism
  • Platelet Activation / drug effects
  • Protein Binding
  • Thrombospondins / drug effects
  • Thrombospondins / metabolism*


  • CD36 Antigens
  • P-Selectin
  • Thrombospondins
  • Calcium