Caspase inhibition of platelet activation

Zoë Cohen, Grace Davis-Gorman, Paul F. McDonagh, Leslie S Ritter

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The role of caspases in platelet function is not well understood. When platelets are activated, they express phosphatidylserine on the outer plasma membrane, form platelet microparticles, and aggregate (Pag). The aims of this study were to determine if caspases play a role in the platelet activation seen in type 2 diabetes. Diabetic rats (Zucker diabetic fatty) were treated with a broad-spectrum caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl ketone, in vivo and platelets were evaluated for phosphatidylserine expression, platelet microparticle formation, and Pag. We found a decreased phosphatidylserine exposure in zVAD-Zucker diabetic fatty rats compared to Zucker diabetic fatty-phosphate-buffered saline when activated with 20 μmol/l ADP. Zucker diabetic fatty rats treated with benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl ketone decreased platelet microparticle numbers compared to phosphate-buffered saline control Zucker diabetic fatty rats. Further, treatment with benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl ketone significantly decreased Pag. These results indicate that caspases play a role in platelet activation, suggesting a unique physiologic role of these proteases and perhaps the underlying mechanisms involved in the chronic platelet activation observed in type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)305-309
Number of pages5
JournalBlood Coagulation and Fibrinolysis
Volume19
Issue number4
DOIs
StatePublished - Jun 2008

Fingerprint

Platelet Activation
Caspases
Blood Platelets
Phosphatidylserines
Ketones
Type 2 Diabetes Mellitus
Phosphates
Zucker Rats
Caspase Inhibitors
Platelet Count
Adenosine Diphosphate
Peptide Hydrolases
Cell Membrane
benzyloxycarbonyl-valyl-alanyl-aspartic acid

Keywords

  • Caspase
  • Diabetes
  • Platelet

ASJC Scopus subject areas

  • Hematology

Cite this

Caspase inhibition of platelet activation. / Cohen, Zoë; Davis-Gorman, Grace; McDonagh, Paul F.; Ritter, Leslie S.

In: Blood Coagulation and Fibrinolysis, Vol. 19, No. 4, 06.2008, p. 305-309.

Research output: Contribution to journalArticle

Cohen, Zoë ; Davis-Gorman, Grace ; McDonagh, Paul F. ; Ritter, Leslie S. / Caspase inhibition of platelet activation. In: Blood Coagulation and Fibrinolysis. 2008 ; Vol. 19, No. 4. pp. 305-309.
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