Étude de molécules brevetées comme agents antiathérosclérotiques dans un modèle murin d’athérosclérose et sur des cellules primaires d’origine humaine

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.