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Ramatroban, a Thromboxane A2 Receptor Antagonist, Prevents Macrophage Accumulation and Neointimal Formation after Balloon Arterial Injury in Cholesterol-fed Rabbits

2003; Lippincott Williams & Wilkins; Volume: 41; Issue: 4 Linguagem: Inglês

10.1097/00005344-200304000-00009

1533-4023

Toshiaki Ishizuka, Kouji Matsumura, Takemi Matsui, Bonpei Takase, Akira Kurita,

Atherosclerosis and Cardiovascular Diseases

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 A2 (TXA2) 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 A2 receptor blockade by ramatroban for 4 weeks after balloon angioplasty in the atherosclerotic rabbits prevented macrophage infiltration through MCP-1 downregulation and neointimal formation.