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BM-573 INHIBITS THE EARLY ATHEROSCLEROTIC LESIONS IN APO-E DEFICIENT MICE BY BLOCKING TP RECEPTORS AND THROMBOXANE SYNTHASE
Cherdon, Céline; Rolin, Stéphanie; Hanson, Julien et al.
2011In Congress of the International Society of Thrombosis and Hemostasis- 57th Annual SSC Meeting
Peer reviewed
 

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Keywords :
TP receptor; Endothelial cells; aspirin; BM-573; cyclooxygenase; isoprostane; thromboxane; adhesion molecule; atherosclerosis
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/Unit :
CREDEC
NTHC
Giga-ULiège
FUNDP
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Cherdon, Céline ;  Université de Liège - ULiège > Département des sciences cliniques > Chirurgie cardio-vasculaire et thoracique
Rolin, Stéphanie
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
Mullier, François
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 EARLY ATHEROSCLEROTIC LESIONS IN APO-E DEFICIENT MICE BY BLOCKING TP RECEPTORS AND THROMBOXANE SYNTHASE
Publication date :
July 2011
Event name :
XXIII Congress of the International Society of Thrombosis and Hemostasis- 57th Annual SSC Meeting Vascular biology
Event organizer :
International Society of Thrombosis and Hemostasis - ISTH
Event place :
Kyoto, Japan
Event date :
July 27, 2011
By request :
Yes
Audience :
International
Main work title :
Congress of the International Society of Thrombosis and Hemostasis- 57th Annual SSC Meeting
Main work alternative title :
[en] ISTH 2011
Peer reviewed :
Peer reviewed
Funders :
FRIA - Fonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture [BE]
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
FRSM - Fonds de la Recherche Scientifique Médicale [BE]
NTHC
CREDEC
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since 31 July 2011

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