Reference : BM-573 inhibits the development of early atherosclerotic lesions in Apo E deficient m...
Scientific journals : Article
Human health sciences : Cardiovascular & respiratory systems
http://hdl.handle.net/2268/87430
BM-573 inhibits the development of early atherosclerotic lesions in Apo E deficient mice by blocking TP receptors and thromboxane synthase.
English
Cherdon, Céline mailto [Université de Liège - ULg > Département des sciences cliniques > Chirurgie cardio-vasculaire et thoracique >]
Rolin, Stephanie mailto [ > > ]
Hanson, Julien mailto [Université de Liège - ULg > Département de pharmacie > Chimie pharmaceutique >]
OOMS, Annie mailto [Centre Hospitalier Universitaire de Liège - CHU > > Chirurgie cardio-vasculaire >]
de Leval, Laurence mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
Drion, Pierre mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R:Méth. expér.des anim. de labo et éth. en expér. anim. >]
Michiels, Carine mailto [ > > ]
Pirotte, Bernard mailto [Université de Liège - ULg > Département de pharmacie > Chimie pharmaceutique >]
Masereel, Bernard mailto [ > > ]
SakalihasanN, Natzi mailto [Centre Hospitalier Universitaire de Liège - CHU > > Chirurgie cardio-vasculaire >]
DEFRAIGNE, Jean mailto [Centre Hospitalier Universitaire de Liège - CHU > > Chirurgie cardio-vasculaire >]
Dogné, Jean-Michel mailto [ > > ]
9-Mar-2011
Prostaglandins & Other Lipid Mediators
Elsevier Science
Yes (verified by ORBi)
International
1098-8823
New York
NY
[en] TP receptor ; atherosclerosis ; adhesion molecule ; thromboxane ; isoprostane ; cyclooxygenase ; BM-573 ; aspirin ; Endothelial cells
[en] 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(2() 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(2(). 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.
CREDEC
Fonds pour la formation à la Recherche dans l'Industrie et dans l'Agriculture (Communauté française de Belgique) - FRIA ; Fonds de la Recherche Scientifique Médicale - FRSM ; Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS
Researchers ; Professionals
http://hdl.handle.net/2268/87430

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