title: Whole blood aggregation and coagulation in db/db and ob/ob mouse models of type 2 diabetes.
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.
authors.affiliation: College of Nursing, University of Arizona, Tucson, Arizona, USA. melissa.henry@unco.edu
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Henry
authors.forename: Lisa B
authors.initials: LB
authors.lastname: Davidson
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Wilson
authors.forename: Brenda K
authors.initials: BK
authors.lastname: McKenna
authors.forename: Sheree A
authors.initials: SA
authors.lastname: Scott
authors.forename: Paul F
authors.initials: PF
authors.lastname: McDonagh
authors.forename: Leslie S
authors.initials: LS
authors.lastname: Ritter
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000235:genetics / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics; D004195:Disease Models, Animal; D051379:Mice; D008820:Mice, Obese / Q000097:blood*; D010974:Platelet Aggregation / Q000235:genetics / Q000502:physiology*; D013916:Thrombelastography; D019851:Thrombophilia / Q000097:blood