Whole blood aggregation and coagulation in db/db and ob/ob mouse models of type 2 diabetes

Melissa L. Henry, Lisa B. Davidson, Jonathan E. Wilson, Brenda K. McKenna, Sheree A. Scott, Paul F. McDonagh, Leslie S. Ritter

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Type 2 diabetes in humans is associated with a significant hypercoagulable state; however, the effects of this on stroke and cardiovascular disease are not completely understood. The genetic mutations in db/db and ob/ob mice produce metabolic abnormalities similar to type 2 diabetes, but little is known about their platelet or coagulation properties. The objective of this study was therefore to examine platelet function and coagulation in db/db and ob/ob mice to determine the degree of alteration induced by type 2 diabetes. Male db/db and ob/ob mice, 8-16 weeks old, and their respective genetic control mice were used for all experiments. To examine platelet function and coagulation, we measured ADP-induced whole blood aggregation at baseline and after inhibition with aspirin and fucoidan, whole blood coagulation by thromboelastography, and platelet CD61 expression by flow cytometry. Both db/db and ob/ob mice demonstrated significantly less ADP-induced whole blood aggregation compared with control mice (db/db mice, P < 0.001; ob/ob mice, P < 0.01). Aggregation was significantly inhibited with aspirin in all groups; however, fucoidan inhibited aggregation only in control mice. The db/db and ob/ob mice demonstrated significantly less maximal clot strength compared with control mice (P < 0.01), and ob/ob mice demonstrated premature clot fibrinolysis measured by thromboelastography. In conclusion, the db/db and ob/ob type 2 diabetes mouse models do not demonstrate a hypercoagulable state similar to humans with this disease. We caution their use for studying cardiovascular and cerebrovascular disease in the setting of type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)124-134
Number of pages11
JournalBlood Coagulation and Fibrinolysis
Volume19
Issue number2
DOIs
StatePublished - Mar 1 2008

Keywords

  • CD61
  • Platelets
  • Thromboelastography
  • Whole blood aggregometry
  • db/db mouse
  • ob/ob mouse

ASJC Scopus subject areas

  • Hematology

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