Affiliation:
1. 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.
Abstract
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) A
2
. The actions of TxA
2
as well as of other arachidonic acid products, such as prostaglandin (PG) H
2
, PGF
2α
, 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 TxA
2
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 TxA
2
metabolite TxB
2
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 TxB
2
levels, indicating the greater efficacy of aspirin in preventing platelet synthesis of TxA
2
. 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 TxA
2
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 TxA
2
, perhaps by preventing the expression of adhesion molecules whose expression is stimulated by eicosanoids other than TxA
2
.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine
Cited by
228 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献