Amyloid Peptide β1-42 Induces Integrin αIIbβ3 Activation, Platelet Adhesion, and Thrombus Formation in a NADPH Oxidase-Dependent Manner
Joint Authors
Abubaker, Aisha Alsheikh
Vara, Dina
Visconte, Caterina
Eggleston, Ian
Canobbio, Ilaria
Pula, Giordano
Torti, Mauro
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-03-14
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
The progression of Alzheimer’s dementia is associated with neurovasculature impairment, which includes inflammation, microthromboses, and reduced cerebral blood flow.
Here, we investigate the effects of β amyloid peptides on the function of platelets, the cells driving haemostasis.
Amyloid peptide β1-42 (Aβ1-42), Aβ1-40, and Aβ25-35 were tested in static adhesion experiments, and it was found that platelets preferentially adhere to Aβ1-42 compared to other Aβ peptides.
In addition, significant platelet spreading was observed over Aβ1-42, while Aβ1-40, Aβ25-35, and the scAβ1-42 control did not seem to induce any platelet spreading, which suggested that only Aβ1-42 activates platelet signalling in our experimental conditions.
Aβ1-42 also induced significant platelet adhesion and thrombus formation in whole blood under venous flow condition, while other Aβ peptides did not.
The molecular mechanism of Aβ1-42 was investigated by flow cytometry, which revealed that this peptide induces a significant activation of integrin αIIbβ3, but does not induce platelet degranulation (as measured by P-selectin membrane translocation).
Finally, Aβ1-42 treatment of human platelets led to detectable levels of protein kinase C (PKC) activation and tyrosine phosphorylation, which are hallmarks of platelet signalling.
Interestingly, the NADPH oxidase (NOX) inhibitor VAS2870 completely abolished Aβ1-42-dependent platelet adhesion in static conditions, thrombus formation in physiological flow conditions, integrin αIIbβ3 activation, and tyrosine- and PKC-dependent platelet signalling.
In summary, this study highlights the importance of NOXs in the activation of platelets in response to amyloid peptide β1-42.
The molecular mechanisms described in this manuscript may play an important role in the neurovascular impairment observed in Alzheimer’s patients.
American Psychological Association (APA)
Abubaker, Aisha Alsheikh& Vara, Dina& Visconte, Caterina& Eggleston, Ian& Torti, Mauro& Canobbio, Ilaria…[et al.]. 2019. Amyloid Peptide β1-42 Induces Integrin αIIbβ3 Activation, Platelet Adhesion, and Thrombus Formation in a NADPH Oxidase-Dependent Manner. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-12.
https://search.emarefa.net/detail/BIM-1202020
Modern Language Association (MLA)
Abubaker, Aisha Alsheikh…[et al.]. Amyloid Peptide β1-42 Induces Integrin αIIbβ3 Activation, Platelet Adhesion, and Thrombus Formation in a NADPH Oxidase-Dependent Manner. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-12.
https://search.emarefa.net/detail/BIM-1202020
American Medical Association (AMA)
Abubaker, Aisha Alsheikh& Vara, Dina& Visconte, Caterina& Eggleston, Ian& Torti, Mauro& Canobbio, Ilaria…[et al.]. Amyloid Peptide β1-42 Induces Integrin αIIbβ3 Activation, Platelet Adhesion, and Thrombus Formation in a NADPH Oxidase-Dependent Manner. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-12.
https://search.emarefa.net/detail/BIM-1202020
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1202020