BICTEL/e - ULg
Serveur institutionnel des thèses de doctorat

• thromboxane ; Récepteur TP/ TP receptor ; molécules d'adhérence/cell adhesion molecules

Atherosclerosis is the first cause of mortality in industrialized countries. This development is influenced by several mediators. Among them, thromboxane A2 (TXA2) and 8-iso-PGF2a have recently received a lot of attention. This study aimed to investigate a dual thromboxane synthase inhibitor and thromboxane receptor antagonist (BM-573) and ASA on lesion formation in apolipoprotein E-deficient mice. The combination of ASA and BM-573 was also studied.

Plasma measurements demonstrated that the treatments did not affect body weight or plasma cholesterol levels. BM-573, but not ASA, significantly decreased atherogenesis lesions as demonstrated by macroscopic analysis. Both treatments alone inhibited TXB2 synthesis but only BM-573 and the combination therapy were able to decrease plasma levels of soluble intracellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1). These results were confirmed on endothelial cells cultures derived from human saphenous vein endothelial cells (HSVECs). In these cells, BM-573 also prevented the increased mRNA expression of ICAM-1 and VCAM-1 induced by U-46619 and 8-iso-PGF2a.

Our results show that a molecule combining receptor antagonism and thromboxane synthase inhibition is more efficient to delay atherosclerosis in Apo E-/- mice than sole inhibition of TXA2 formation.

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