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Thesis

English

ID: <

10670/1.w23ixf

>

Where these data come from
Lipid rafts of platelet membrane as therapeutic target : role of "Omics"

Abstract

Latelets are blood ce lis at the crossroads of both haemostasis and thrombosis. The majority of platelet functions depend on their membrane, which contains numerous, ordered lipid microdomains named lipid rafts. These microdomains play a pivotai role in all phases of plateletmediated haemostasis. Lipid rafts are a prerequisite for the functioning of receptors in charge of platelet activation and signal transduction. The role of platelets in thrombotic diseases is crucial, and underpins the continue research interest in antiplatelet therapy. ln this context, we aimed to study the lipid rafts of platelet membranes as the principal assembly place of known receptors, and likely also other, unknown elements that participate in the thrombotic function of platelets, with a view to proposing new therapeutic targets. We used lipidomics and proteomics as well as immunoblot analysis to identify lipid rafts and investigate the organization of lipid rafts in resting, stimulated and antiplatelet-treated platelets. Detergents, ultracentrifugation and sucrose gradients were used mainly for membrane fractionatio and isolation of lipid rafts. The main findings of our work are: 1) Development of a framework or guidelines for platelet lipid raft investigation; 2) Presentation of a global profile of the lipid and protein composition of plate let lipid rafts; 3) Demonstration of the impact of activators and inhibitors on the reorganization of platelet lipid rafts; and 4) Suggestion for potential new therapeutic targets by proteomics analysis through interactive network analyzing of coagulation factor XIII (FXIII) and Vasodilator-Stimulated Phosphoprotein (VASP). Our results show that lipid rafts have potential as new therapeutic targets in pharmacological research in antiplatelets. "Omics" studies are important to expand our knowledge in this field

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