Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:1724-1728
© 2000 American Heart Association, Inc.
Vascular Biology |
The Thromboxane Receptor Antagonist S18886 but Not Aspirin Inhibits Atherogenesis in Apo E–Deficient Mice
Evidence That Eicosanoids Other Than Thromboxane Contribute to Atherosclerosis
From the Vascular Biology Unit (A.J.C., Y.D., J.O.-K., R.A.C.), Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Mass, and Institut de Recherche Servier (G.L., T.J.V.), Suresnes, France.
Correspondence to Richard A. Cohen, MD, Vascular Biology Unit R408, Boston University Medical Center, 80 E Concord St, Boston, MA 02118. E-mail racohen{at}med-med1.bu.edu
Abstract—Atherosclerosis
involves a complex array of factors, including leukocyte adhesion and
platelet vasoactive factors. Aspirin, which is used to prevent
secondary complications of atherosclerosis, inhibits
platelet production of thromboxane (Tx)
A2. The actions of TxA2 as
well as of other arachidonic acid products, such as
prostaglandin (PG) H2,
PGF2
,
hydroxyeicosatetraenoic acids, and
isoprostanes, can be effectively antagonized by blocking
thromboxane (TP) receptors. The purpose of this study was
to determine the role of platelet-derived
TxA2 in atherosclerotic lesion development by
comparing the effects of aspirin and the TP receptor
antagonist S18886. The effect of 11 weeks of treatment with
aspirin (30 mg · kg-1 ·
d-1) or S18886 (5 mg ·
kg-1 · d-1) on
aortic root atherosclerotic lesions, serum levels of intercellular
adhesion molecule-1 (ICAM-1), and the TxA2
metabolite TxB2 was determined in apolipoprotein
E–deficient mice at 21 weeks of age. Both treatments did not affect
body or heart weight or serum cholesterol levels. Aspirin,
to a greater extent than S18886, significantly decreased serum
TxB2 levels, indicating the greater efficacy of
aspirin in preventing platelet synthesis of
TxA2. S18886, but not aspirin, significantly
decreased aortic root lesions as well as serum ICAM-1 levels. S18886
also prevented the increased expression of ICAM-1 in cultured human
endothelial cells stimulated by the TP receptor agonist
U46619. These results indicate that inhibition of platelet
TxA2 synthesis with aspirin has no significant
effect on atherogenesis or adhesion molecule levels. The effects of
S18886 suggest that blockade of TP receptors inhibits
atherosclerosis by a mechanism independent of
platelet-derived TxA2, perhaps by preventing
the expression of adhesion molecules whose expression is stimulated by
eicosanoids other than TxA2.
Key Words: thromboxane receptor • atherosclerosis • aspirin • adhesion • thromboxane
This article has been cited by other articles:
 |
|
 |
|
  H. Bayat, S. Xu, D. Pimentel, R. A. Cohen, and B. Jiang Activation of Thromboxane Receptor Upregulates Interleukin (IL)-1 Induced VCAM-1 Expression Through JNK Signaling Arterioscler. Thromb. Vasc. Biol., January 1, 2008; 28(1): 127 - 134. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Michel, S. Simonet, C. Vayssettes-Courchay, F. Bertin, P. Sansilvestri-Morel, F. Bernhardt, J. Paysant, J.-S. Silvestre, B. I. Levy, M. Feletou, et al. Altered TP receptor function in isolated, perfused kidneys of nondiabetic and diabetic ApoE-deficient mice Am J Physiol Renal Physiol, January 1, 2008; 294(1): F120 - F129. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Habib, I. Shamseddeen, M. S. Nasrallah, T. A. Antoun, G. Nemer, J. Bertoglio, R. Badreddine, and K. F. Badr Modulation of COX-2 expression by statins in human monocytic cells FASEB J, June 1, 2007; 21(8): 1665 - 1674. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Meadows and D. L. Bhatt Clinical Aspects of Platelet Inhibitors and Thrombus Formation Circ. Res., May 11, 2007; 100(9): 1261 - 1275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Cyrus, Y. Yao, T. Ding, J. M. Dogne, and D. Pratico Thromboxane receptor blockade improves the antiatherogenic effect of thromboxane A2 suppression in LDLR KO mice Blood, April 15, 2007; 109(8): 3291 - 3296. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Sebekova, T. Eifert, A. Klassen, A. Heidland, and K. Amann Renal Effects of S18886 (Terutroban), a TP Receptor Antagonist, in an Experimental Model of Type 2 Diabetes Diabetes, April 1, 2007; 56(4): 968 - 974. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Michel, J.-S. Silvestre, L. Waeckel, S. Corda, T. Verbeuren, J. P. Vilaine, M. Clergue, M. Duriez, and B. I. Levy Thromboxane A2/Prostaglandin H2 Receptor Activation Mediates Angiotensin II-Induced Postischemic Neovascularization Arterioscler. Thromb. Vasc. Biol., March 1, 2006; 26(3): 488 - 493. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. R. Babaev, L. Ding, J. Reese, J. D. Morrow, M. D. Breyer, S. K. Dey, S. Fazio, and M. F. Linton Cyclooxygenase-1 Deficiency in Bone Marrow Cells Increases Early Atherosclerosis in Apolipoprotein E- and Low-Density Lipoprotein Receptor-Null Mice Circulation, January 3, 2006; 113(1): 108 - 117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Xu, B. Jiang, K. A. Maitland, H. Bayat, J. Gu, J. L. Nadler, S. Corda, G. Lavielle, T. J. Verbeuren, A. Zuccollo, et al. The Thromboxane Receptor Antagonist S18886 Attenuates Renal Oxidant Stress and Proteinuria in Diabetic Apolipoprotein E-Deficient Mice Diabetes, January 1, 2006; 55(1): 110 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zuccollo, C. Shi, R. Mastroianni, K. A. Maitland-Toolan, R. M. Weisbrod, M. Zang, S. Xu, B. Jiang, J. M. Oliver-Krasinski, A. J. Cayatte, et al. The Thromboxane A2 Receptor Antagonist S18886 Prevents Enhanced Atherogenesis Caused by Diabetes Mellitus Circulation, November 8, 2005; 112(19): 3001 - 3008. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tang, T. Cyrus, Y. Yao, L. Vocun, and D. Pratico Involvement of Thromboxane Receptor in the Proatherogenic Effect of Isoprostane F2{alpha}-III: Evidence From Apolipoprotein E- and LDL Receptor-Deficient Mice Circulation, November 1, 2005; 112(18): 2867 - 2874. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Antman, D. DeMets, and J. Loscalzo Cyclooxygenase Inhibition and Cardiovascular Risk Circulation, August 2, 2005; 112(5): 759 - 770. [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Viles-Gonzalez, V. Fuster, R. Corti, C. Valdiviezo, R. Hutter, S. Corda, S. X. Anand, and J. J. Badimon Atherosclerosis regression and TP receptor inhibition: effect of S18886 on plaque size and composition--a magnetic resonance imaging study Eur. Heart J., August 1, 2005; 26(15): 1557 - 1561. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Libby and P. Theroux Pathophysiology of Coronary Artery Disease Circulation, June 28, 2005; 111(25): 3481 - 3488. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Hanson, S. Rolin, D. Reynaud, N. Qiao, L. P. Kelley, H. M. Reid, F. Valentin, J. Tippins, B. T. Kinsella, B. Masereel, et al. In Vitro and in Vivo Pharmacological Characterization of BM-613 [N-n-Pentyl-N'-[2-(4'-methylphenylamino)-5-nitrobenzenesulfonyl]urea], a Novel Dual Thromboxane Synthase Inhibitor and Thromboxane Receptor Antagonist J. Pharmacol. Exp. Ther., April 1, 2005; 313(1): 293 - 301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Egan, M. Wang, M. B. Lucitt, A. M. Zukas, E. Pure, J. A. Lawson, and G. A. FitzGerald Cyclooxygenases, Thromboxane, and Atherosclerosis: Plaque Destabilization by Cyclooxygenase-2 Inhibition Combined With Thromboxane Receptor Antagonism Circulation, January 25, 2005; 111(3): 334 - 342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Fries and T. Grosser The Cardiovascular Pharmacology of COX-2 Inhibition Hematology, January 1, 2005; 2005(1): 445 - 451. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Wilson, A. M. Roche, E. Kostetskaia, and E. M. Smyth Dimerization of the Human Receptors for Prostacyclin and Thromboxane Facilitates Thromboxane Receptor-mediated cAMP Generation J. Biol. Chem., December 17, 2004; 279(51): 53036 - 53047. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-L. Cracowski and O. Ormezzano Isoprostanes, emerging biomarkers and potential mediators in cardiovascular diseases Eur. Heart J., October 1, 2004; 25(19): 1675 - 1678. [Full Text] [PDF]
|
|
|
|
|
|
E. Torsney, U. Mayr, Y. Zou, W. D. Thompson, Y. Hu, and Q. Xu Thrombosis and Neointima Formation in Vein Grafts Are Inhibited by Locally Applied Aspirin Through Endothelial Protection Circ. Res., June 11, 2004; 94(11): 1466 - 1473. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bolla, D. You, L. Loufrani, B. I. Levy, S. Levy-Toledano, A. Habib, and D. Henrion Cyclooxygenase Involvement in Thromboxane-Dependent Contraction in Rat Mesenteric Resistance Arteries Hypertension, June 1, 2004; 43(6): 1264 - 1269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lepantalo, K. S Virtanen, J. Heikkila, U. Wartiovaara, and R. Lassila Limited early antiplatelet effect of 300 mg clopidogrel in patients with aspirin therapy undergoing percutaneous coronary interventions Eur. Heart J., March 2, 2004; 25(6): 476 - 483. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Dwyer, H. Allayee, K. M. Dwyer, J. Fan, H. Wu, R. Mar, A. J. Lusis, and M. Mehrabian Arachidonate 5-Lipoxygenase Promoter Genotype, Dietary Arachidonic Acid, and Atherosclerosis N. Engl. J. Med., January 1, 2004; 350(1): 29 - 37. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. A. Belton, A. Duffy, S. Toomey, and D. J. Fitzgerald Cyclooxygenase Isoforms and Platelet Vessel Wall Interactions in the Apolipoprotein E Knockout Mouse Model of Atherosclerosis Circulation, December 16, 2003; 108(24): 3017 - 3023. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Hankey and J. W. Eikelboom Cyclooxygenase-2 Inhibitors: Are They Really Atherothrombotic, and If Not, Why Not? Stroke, November 1, 2003; 34(11): 2736 - 2740. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Fujii, L. Zhang, J. Igarashi, and H. Kosaka L-Arginine Reverses p47phox and gp91phox Expression Induced by High Salt in Dahl Rats Hypertension, November 1, 2003; 42(5): 1014 - 1020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Griendling and G. A. FitzGerald Oxidative Stress and Cardiovascular Injury: Part II: Animal and Human Studies Circulation, October 28, 2003; 108(17): 2034 - 2040. [Full Text] [PDF]
|
|
|
|
 |
|
 B. OSTERUD and E. BJORKLID Role of Monocytes in Atherogenesis Physiol Rev, October 1, 2003; 83(4): 1069 - 1112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J-L Cracowski The putative role of isoprostanes in human cardiovascular physiology and disease: following the fingerprints Heart, August 1, 2003; 89(8): 821 - 822. [Full Text] [PDF]
|
|
|
|
 |
|
 L. Belhassen, G. Pelle, J.-L. Dubois-Rande, and S. Adnot Improved endothelial function by the thromboxane a2 receptor antagonist s 18886 in patients with coronary artery disease treated with aspirin J. Am. Coll. Cardiol., April 2, 2003; 41(7): 1198 - 1204. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Prasad and P. Lee Suppression of Oxidative Stress as a Mechanism of Reduction of Hypercholesterolemic Atherosclerosis by Aspirin Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2003; 8(1): 61 - 69. [Abstract] [PDF]
|
|
|
|
|
|
D. Yang, M. Feletou, N. Levens, J. N. Zhang, and P. M. Vanhoutte A Diffusible Substance(s) Mediates Endothelium-Dependent Contractions in the Aorta of SHR Hypertension, January 1, 2003; 41(1): 143 - 148. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Cyrus, S. Sung, L. Zhao, C. D. Funk, S. Tang, and D. Pratico Effect of Low-Dose Aspirin on Vascular Inflammation, Plaque Stability, and Atherogenesis in Low-Density Lipoprotein Receptor-Deficient Mice Circulation, September 3, 2002; 106(10): 1282 - 1287. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-E. Eilertsen and B. Osterud The central role of thromboxane and platelet activating factor receptors in ex vivo regulation of endotoxin-induced monocyte tissue factor activity in human whole blood Innate Immunity, August 1, 2002; 8(4): 285 - 293. [Abstract] [PDF]
|
|
|
|
|
|
M. K. Halushka and P. V. Halushka Why Are Some Individuals Resistant to the Cardioprotective Effects of Aspirin?: Could It Be Thromboxane A2? Circulation, April 9, 2002; 105(14): 1620 - 1622. [Full Text] [PDF]
|
|
|
|
|
|
E. Connolly, D. J. Bouchier-Hayes, E. Kaye, A. Leahy, D. Fitzgerald, and O. Belton Cyclooxygenase Isozyme Expression and Intimal Hyperplasia in a Rat Model of Balloon Angioplasty J. Pharmacol. Exp. Ther., February 1, 2002; 300(2): 393 - 398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-H. Zou, C. Shi, and R. A. Cohen High Glucose via Peroxynitrite Causes Tyrosine Nitration and Inactivation of Prostacyclin Synthase That Is Associated With Thromboxane/Prostaglandin H2 Receptor-Mediated Apoptosis and Adhesion Molecule Expression in Cultured Human Aortic Endothelial Cells Diabetes, January 1, 2002; 51(1): 198 - 203. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Cyrus, L. X. Tang, J. Rokach, G. A. FitzGerald, and D. Pratico Lipid Peroxidation and Platelet Activation in Murine Atherosclerosis Circulation, October 16, 2001; 104(16): 1940 - 1945. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Cayatte, A. Rupin, J. Oliver-Krasinski, K. Maitland, P. Sansilvestri-Morel, M.-F. Boussard, M. Wierzbicki, T. J. Verbeuren, and R. A. Cohen S17834, a New Inhibitor of Cell Adhesion and Atherosclerosis That Targets NADPH Oxidase Arterioscler. Thromb. Vasc. Biol., October 1, 2001; 21(10): 1577 - 1584. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Unmack, P. K. Rangachari, and E. Skadhauge Effects of Isoprostanes and Prostanoids on Porcine Small Intestine J. Pharmacol. Exp. Ther., April 13, 2001; 296(2): 434 - 441. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. Praticò, C. Tillmann, Z.-B. Zhang, H. Li, and G. A. FitzGerald Acceleration of atherogenesis by COX-1-dependent prostanoid formation in low density lipoprotein receptor knockout mice PNAS, March 1, 2001; (2001) 61607398. [Abstract] [Full Text]
|
|
|
|
|
|
L. Fontana, C. Giagulli, P. Minuz, A. Lechi, and C. Laudanna 8-Iso-PGF2{{alpha}} Induces {beta}2-Integrin-Mediated Rapid Adhesion of Human Polymorphonuclear Neutrophils : A Link Between Oxidative Stress and Ischemia/Reperfusion Injury Arterioscler. Thromb. Vasc. Biol., January 1, 2001; 21(1): 55 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Pratico, Y. Cheng, and G. A. FitzGerald TP or Not TP: Primary Mediators in a Close Runoff? Arterioscler. Thromb. Vasc. Biol., July 1, 2000; 20(7): 1695 - 1698. [Full Text] [PDF]
|
|
|
|
|
|
D. Pratico, C. Tillmann, Z.-B. Zhang, H. Li, and G. A. FitzGerald Acceleration of atherogenesis by COX-1-dependent prostanoid formation in low density lipoprotein receptor knockout mice PNAS, March 13, 2001; 98(6): 3358 - 3363. [Abstract] [Full Text] [PDF]
|
|