Skip to Main content Skip to Navigation
Theses

Etude des mécanismes d'adhérence et d'activation des plaquettes sanguines appliquée à l'identification de nouvelles cibles anti-thrombotiques plus sûres

Abstract : Following vascular injury, blood platelet adhesion, activation and aggregation are essential for hemostasis but can also lead to arterial thrombosis, which is a leading cause of death worldwide. Current antithrombotic drugs impede platelet activation and aggregation, thereby considerably reducing cardiovascular mortality, but their use is linked to an increased bleeding risk. This thesis aimed to explore more selective strategies causing minimal perturbation of hemostasis. The use of genetically-modified mice has revealed an unsuspected important contribution of integrin alpha6 beta1, which mediates platelet adhesion to laminins, to experimental arterial thrombosis but not hemostasis. In addition, we showed that tenascin-C, an extracellular matrix protein overexpressed in atherosclerotic plaques, can support platelet adhesion and activation under flow. In contrast, the signaling protein beta-arrestin-1 does not play a major role in platelet function, hemostasis and thrombosis. In conclusion, this work provides two interesting candidates, namely integrin alpha6 beta1 and tenascin-C, to put into practice the concept of targeting thrombosis while minimally impairing hemostasis.
Complete list of metadatas

https://tel.archives-ouvertes.fr/tel-00867777
Contributor : Abes Star :  Contact
Submitted on : Monday, September 30, 2013 - 3:07:10 PM
Last modification on : Friday, December 4, 2020 - 3:10:05 PM

File

Schaff_Mathieu_2012_ED414.pdf
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-00867777, version 1

Collections

Citation

Mathieu Schaff. Etude des mécanismes d'adhérence et d'activation des plaquettes sanguines appliquée à l'identification de nouvelles cibles anti-thrombotiques plus sûres. Hématologie. Université de Strasbourg, 2012. Français. ⟨NNT : 2012STRAJ102⟩. ⟨tel-00867777⟩

Share

Metrics

Record views

730

Files downloads

15271