The Thromboxane Receptor Antagonist S18886 but Not Aspirin Inhibits Atherogenesis in Apo E–Deficient Mice

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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, PGF2α, 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...