It has been known that vascular inflammatory reactions, such as adherence and infiltration of monocytes and lymphocytes into the vascular endothelium, play an important role in the pathogenesis of atherosclerosis. In this process, the expression of adhesion molecules and chemokines is responsible in the vascular endothelium. In human and animal athero- sclerotic tissues, the expression of thromboxane A2 (TXA2) and F2-isoprostane, ligands of TXA2 receptors, is potentiated, suggesting the involvement of these factors in atherosclerosis. Several in vitro studies suggest that stimulation of TXA2 receptors in vascular endothelial cells may augment expression of adhesion molecules and chemokines. TXA2 receptor antagonists may prevent the exacerbation of inflammation by blocking these responses. Recent reports using experimental animal models of atherosclerosis indicated that the induction of adhesion molecule and chemokine expression by TXA2 receptor stimulation is significantly involved in the process of inflammatory cell infiltration in the formation of atherosclerotic lesions. It is understood that TXA2 receptor antagonists inhibit the formation of this lesion by blocking the process. It has been clinically proven that low-dose aspirin, a cyclooxygenase inhibitor and an agent to inhibit TXA2 formation, prevents cardiovascular events following an intervention. However, low-dose aspirin do not inhibit the production of F2- isoprostanes by oxidative stress in the atherosclerotic lesions. In this regard, potent TXA2 receptor antagonists are capable of blocking the actions of TXA2 and F2-isoprostane, thus may offer a more potent effect in the prevention of atherosclerotic vascular diseases.
Keywords: Atherosclerosis, TXA2, F2-isoprostane, adhesion molecules, monocyte chemoattractant protein-1, macrophage infiltration, restenosis, vascular dysfunction