Article (Scientific journals)
BM-573 inhibits the development of early atherosclerotic lesions in Apo E deficient mice by blocking TP receptors and thromboxane synthase.
Cherdon, Céline; Rolin, Stephanie; Hanson, Julien et al.
2011In Prostaglandins and Other Lipid Mediators
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Keywords :
TP receptor; atherosclerosis; adhesion molecule; thromboxane; isoprostane; cyclooxygenase; BM-573; aspirin; Endothelial cells
Abstract :
[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.
Research center :
CREDEC
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Cherdon, Céline ;  Université de Liège - ULiège > Département des sciences cliniques > Chirurgie cardio-vasculaire et thoracique
Rolin, Stephanie
Hanson, Julien  ;  Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique
OOMS, Annie ;  Centre Hospitalier Universitaire de Liège - CHU > Chirurgie cardio-vasculaire
de Leval, Laurence ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Drion, Pierre ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R:Méth. expér.des anim. de labo et éth. en expér. anim.
Michiels, Carine
Pirotte, Bernard ;  Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique
Masereel, Bernard
SakalihasanN, Natzi ;  Centre Hospitalier Universitaire de Liège - CHU > Chirurgie cardio-vasculaire
DEFRAIGNE, Jean ;  Centre Hospitalier Universitaire de Liège - CHU > Chirurgie cardio-vasculaire
Dogné, Jean-Michel
Language :
English
Title :
BM-573 inhibits the development of early atherosclerotic lesions in Apo E deficient mice by blocking TP receptors and thromboxane synthase.
Publication date :
09 March 2011
Journal title :
Prostaglandins and Other Lipid Mediators
ISSN :
1098-8823
Publisher :
Elsevier Science, New York, United States - New York
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
FRIA - Fonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture [BE]
FRSM - Fonds de la Recherche Scientifique Médicale [BE]
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
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