Bleeding is increased in amyloid precursor protein knockout mouse.

Autor: Mazinani N; Michael Smith Laboratories University of British Columbia Vancouver BC Canada.; Centre for Blood Research University of British Columbia Vancouver BC Canada.; Department of Biochemistry and Molecular Biology University of British Columbia Vancouver BC Canada., Strilchuk AW; Michael Smith Laboratories University of British Columbia Vancouver BC Canada.; Centre for Blood Research University of British Columbia Vancouver BC Canada.; Department of Biochemistry and Molecular Biology University of British Columbia Vancouver BC Canada., Baylis JR; Michael Smith Laboratories University of British Columbia Vancouver BC Canada.; Biomedical Engineering Program University of British Columbia Vancouver BC Canada., Hur WS; Michael Smith Laboratories University of British Columbia Vancouver BC Canada.; Centre for Blood Research University of British Columbia Vancouver BC Canada.; Department of Biochemistry and Molecular Biology University of British Columbia Vancouver BC Canada., Jefferies WA; Michael Smith Laboratories University of British Columbia Vancouver BC Canada.; Department of Medical Genetics University of British Columbia Vancouver BC Canada., Kastrup CJ; Michael Smith Laboratories University of British Columbia Vancouver BC Canada.; Centre for Blood Research University of British Columbia Vancouver BC Canada.; Department of Biochemistry and Molecular Biology University of British Columbia Vancouver BC Canada.
Jazyk: angličtina
Zdroj: Research and practice in thrombosis and haemostasis [Res Pract Thromb Haemost] 2020 Jun 14; Vol. 4 (5), pp. 823-828. Date of Electronic Publication: 2020 Jun 14 (Print Publication: 2020).
DOI: 10.1002/rth2.12375
Abstrakt: Background: Amyloid precursor protein (APP) is highly expressed in platelets. APP is the precursor to amyloid beta (Aβ) peptides that accumulate in cerebral amyloid angiopathy and plaques in Alzheimer disease. APP and its metabolites interact with many components of the coagulation system, and have both anticoagulant and procoagulant properties, but it is unclear if APP contributes to hemostasis in vivo.
Objectives: To determine whether APP contributes to hemostasis in mice, including when inhibitors of coagulation are administered.
Methods: Blood loss in APP knockout (KO) mice was measured in liver laceration and tail transection models of hemorrhage. Blood loss was also measured following tail transection in mice given an inhibitor of coagulation factor Xa (apixaban), platelet inhibitors (aspirin + clopidogrel), tissue-type plasminogen activator (t-PA), or the antifibrinolytic tranexamic acid (TXA).
Results and Discussion: Blood loss from liver lacerations was similar between APP KO mice and wild-type (WT) mice, but APP KO mice bled more from tail transections. When mice were challenged with aspirin + clopidogrel, the difference in bleeding between APP KO and WT mice was abrogated. In contrast, a difference in bleeding between the strains persisted when mice were treated with apixaban, t-PA, or TXA. Blood collected from APP KO mice and analyzed with thromboelastography had longer clotting times, and the clots were less stiff and more susceptible to fibrinolysis compared to blood from WT mice.
Conclusions: The absence of APP measurably increases bleeding in mice, which is consistent with a role for platelet-derived APP and Aβ peptides in hemostasis.
(© 2020 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)
Databáze: MEDLINE
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