Ramatroban,a thromboxane A2 receptor antagonist,prevents macrophage accumulation and neointimal formation after balloon arterial injury in cholesterol-fed rabbits

Macrophage infiltration appears to play an important role in restenosis after arterial intervention. Monocyte chemoattractant protein-1 (MCP-1) is a major chemotactic factor for macrophages. We have previously shown that ramatroban, a thromboxane A(2) (TXA(2)) receptor antagonist, diminished the expression of MCP-1 in human vascular endothelial cells. The aim of this study was to evaluate whether, after balloon angioplasty of atherosclerotic arteries, ramatroban would reduce MCP-1 expression, macrophage accumulation, and neointimal formation. New Zealand white rabbits were fed a cholesterol-rich diet for 4 weeks, and the abdominal aorta of the rabbits were injured by a 2-French Fogarty catheter. They were randomized to receive 1 or 5 mg/kg daily of ramatroban (n = 7 or n = 8) or saline (n = 6). At 4 weeks after balloon angioplasty, the intimal hyperplasia and the macrophage-positive area in the intima by the ramatroban treatment was significantly reduced. Monocyte chemoattractant protein-1 gene expression in injured aortas of the ramatroban-treated group was significantly less evident than in the vehicle-treated group. Thromboxane A(2) receptor blockade by ramatroban for 4 weeks after balloon angioplasty in the atherosclerotic rabbits prevented macrophage infiltration through MCP-1 downregulation and neointimal formation.