Titre
BM-573 inhibits the development of early atherosclerotic lesions in Apo E deficient mice by blocking TP receptors and thromboxane synthase.
Type
article
Institution
Externe
Périodique
Auteur(s)
Cherdon, C.
Auteure/Auteur
Rolin, S.
Auteure/Auteur
Hanson, J.
Auteure/Auteur
Ooms, A.
Auteure/Auteur
de Leval, L.
Auteure/Auteur
Drion, P.
Auteure/Auteur
Michiels, C.
Auteure/Auteur
Pirotte, B.
Auteure/Auteur
Masereel, B.
Auteure/Auteur
Sakalihassan, N.
Auteure/Auteur
Defraigne, J.O.
Auteure/Auteur
Dogné, J.M.
Auteure/Auteur
Liens vers les personnes
ISSN
1098-8823
Statut éditorial
Publié
Date de publication
2011
Volume
94
Numéro
3-4
Première page
124
Dernière page/numéro d’article
132
Peer-reviewed
Oui
Langue
anglais
Résumé
Atherosclerosis is the principal cause of mortality in industrialized countries. Its development is influenced by several mediators of which thromboxane A(2) (TXA(2)) and 8-iso-PGF(2α) have recently received a lot of attention. This study aimed to investigate the effect of 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 atherogenic lesions as demonstrated by macroscopic analysis. Both treatments alone inhibited TXB(2) synthesis but only BM-573 and the combination therapy were able to decrease firstly, plasma levels of soluble intracellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) and secondly, the expression of these proteins in the aortic root of Apo E. These results were confirmed in endothelial cell 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-PGF(2α). Our results show that a molecule combining receptor antagonism and thromboxane synthase inhibition is more efficient in delaying atherosclerosis in Apo E(-/-) mice than sole inhibition of TXA(2) formation.
Sujets
PID Serval
serval:BIB_6F47590285BF
PMID
Date de création
2012-02-29T09:36:22.658Z
Date de création dans IRIS
2025-05-21T00:33:09Z