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Comprehensive Analysis of Procoagulant Platelets Exhibiting Features of Necrosis, Apoptosis and Platelet Activation
Published on: May 23, 2025
Activation of human platelets by misfolded proteins
Eszter Herczenik1, Barend Bouma, Suzanne J A Korporaal
1Laboratory of Thrombosis and Haemostasis, Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
Arteriosclerosis, Thrombosis, and Vascular Biology
|May 19, 2007
Summary
Misfolded proteins forming amyloid fibrils trigger platelet aggregation, a key process in various diseases. This amyloid-induced platelet activation involves specific molecular pathways, explaining heightened platelet activity in amyloidosis.
Area of Science:
- Biochemistry
- Hematology
- Pathology
Background:
- Protein misfolding leads to amyloid deposition in diseases like Alzheimer's.
- Platelet activation is potentially implicated in amyloid-related pathologies.
Purpose of the Study:
- To investigate if amyloid fibrils induce platelet aggregation.
- To elucidate the mechanisms of amyloid-mediated platelet activation.
Main Methods:
- Induced amyloid properties in six proteins.
- Assessed platelet aggregation and identified involved pathways (CD36, p38 MAPK, glycoprotein Ib alpha).
- Utilized specific inhibitors and genetic modifications (e.g., CD36-/- mice).
Main Results:
- All induced amyloid proteins caused platelet aggregation.
- Aggregation was independent of initial thromboxane A2 and ADP release but enhanced by feedback.
- Inhibitors targeting cAMP, Ca2+, CD36, p38 MAPK, COX-1, and glycoprotein Ib alpha demonstrated varying degrees of inhibition.
- AlphaIIb beta3-independent aggregation (agglutination) was observed.
Conclusions:
- Amyloid formation directly induces platelet aggregation.
- Two primary pathways mediate amyloid-induced platelet activation: CD36/p38 MAPK/thromboxane A2 and glycoprotein Ib alpha.
- These findings may explain increased platelet activation in diseases with amyloid deposits.
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