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.
Ishizuka
Toshiaki
T
Department of Medical Engineering, National Defense Medical College, Tokorozawa, Saitama, Japan. TIR2@aol.com
Matsumura
Kouji
K
Matsui
Takemi
T
Takase
Bonpei
B
Kurita
Akira
A
D000800:Angioplasty, Balloon / Q000009:adverse effects* / Q000379:methods; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002227:Carbazoles / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D002784:Cholesterol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008264:Macrophages / Q000187:drug effects* / Q000473:pathology; D008297:Male; D011817:Rabbits; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology*; D017539:Tunica Intima / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D002227:Carbazoles; D018932:Chemokine CCL2; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D002784:Cholesterol; C063119:ramatroban