Amyloid precursor protein is required for in vitro platelet adhesion to amyloid peptides and potentiation of thrombus formation
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Amyloid precursor protein is required for in vitro platelet adhesion to amyloid peptides and potentiation of thrombus formation. / Visconte, Caterina; Canino, Jessica; Guidetti, Gianni Francesco; Zarà, Marta; Seppi, Claudio; Abubaker, Aisha Alsheikh; Pula, Giordano; Torti, Mauro; Canobbio, Ilaria.
in: CELL SIGNAL, Jahrgang 52, 12.2018, S. 95-102.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Amyloid precursor protein is required for in vitro platelet adhesion to amyloid peptides and potentiation of thrombus formation
AU - Visconte, Caterina
AU - Canino, Jessica
AU - Guidetti, Gianni Francesco
AU - Zarà, Marta
AU - Seppi, Claudio
AU - Abubaker, Aisha Alsheikh
AU - Pula, Giordano
AU - Torti, Mauro
AU - Canobbio, Ilaria
N1 - Copyright © 2018 Elsevier Inc. All rights reserved.
PY - 2018/12
Y1 - 2018/12
N2 - Amyloid precursor protein (APP) is the precursor of amyloid β (Aβ) peptides, whose accumulation in the brain is associated with Alzheimer's disease. APP is also expressed on the platelet surface and Aβ peptides are platelet agonists. The physiological role of APP is largely unknown. In neurons, APP acts as an adhesive receptor, facilitating integrin-mediated cell adhesion, while in platelets it regulates coagulation and venous thrombosis. In this work, we analyzed platelets from APP KO mice to investigate whether membrane APP supports platelet adhesion to physiological and pathological substrates. We found that APP-null platelets adhered and spread normally on collagen, von Willebrand Factor or fibrinogen. However, adhesion on immobilized Aβ peptides Aβ1-40, Aβ1-42 and Aβ25-35 was completely abolished in platelets lacking APP. By contrast, platelet activation and aggregation induced by Aβ peptides occurred normally in the absence of APP. Adhesion of APP-transfected HEK293 to Aβ peptides was significantly higher than that of control cells expressing low levels of APP. Co-coating of Aβ1-42 and Aβ25-35 with collagen strongly potentiated platelet adhesion when whole blood from wild type mice was perfused at arterial shear rate, but had no effects with blood from APP KO mice. These results demonstrate that APP selectively mediates platelet adhesion to Aβ under static condition but not platelet aggregation, and is responsible for Aβ-promoted potentiation of thrombus formation under flow. Therefore, APP may facilitate an early step in thrombus formation when Aβ peptides accumulate in cerebral vessel walls or atherosclerotic plaques.
AB - Amyloid precursor protein (APP) is the precursor of amyloid β (Aβ) peptides, whose accumulation in the brain is associated with Alzheimer's disease. APP is also expressed on the platelet surface and Aβ peptides are platelet agonists. The physiological role of APP is largely unknown. In neurons, APP acts as an adhesive receptor, facilitating integrin-mediated cell adhesion, while in platelets it regulates coagulation and venous thrombosis. In this work, we analyzed platelets from APP KO mice to investigate whether membrane APP supports platelet adhesion to physiological and pathological substrates. We found that APP-null platelets adhered and spread normally on collagen, von Willebrand Factor or fibrinogen. However, adhesion on immobilized Aβ peptides Aβ1-40, Aβ1-42 and Aβ25-35 was completely abolished in platelets lacking APP. By contrast, platelet activation and aggregation induced by Aβ peptides occurred normally in the absence of APP. Adhesion of APP-transfected HEK293 to Aβ peptides was significantly higher than that of control cells expressing low levels of APP. Co-coating of Aβ1-42 and Aβ25-35 with collagen strongly potentiated platelet adhesion when whole blood from wild type mice was perfused at arterial shear rate, but had no effects with blood from APP KO mice. These results demonstrate that APP selectively mediates platelet adhesion to Aβ under static condition but not platelet aggregation, and is responsible for Aβ-promoted potentiation of thrombus formation under flow. Therefore, APP may facilitate an early step in thrombus formation when Aβ peptides accumulate in cerebral vessel walls or atherosclerotic plaques.
KW - Alzheimer Disease/metabolism
KW - Amyloid beta-Peptides/metabolism
KW - Amyloid beta-Protein Precursor/genetics
KW - Animals
KW - Blood Platelets/metabolism
KW - Cell Adhesion
KW - HEK293 Cells
KW - Humans
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Platelet Activation
KW - Platelet Adhesiveness
KW - Platelet Aggregation
KW - Thrombosis/metabolism
U2 - 10.1016/j.cellsig.2018.08.017
DO - 10.1016/j.cellsig.2018.08.017
M3 - SCORING: Journal article
C2 - 30172024
VL - 52
SP - 95
EP - 102
JO - CELL SIGNAL
JF - CELL SIGNAL
SN - 0898-6568
ER -