Trapidil inhibits monocyte chemoattractant protein-1 and macrophage accumulation after balloon arterial injury in rabbits.
Trapidil (triazolopyrimidine) is an antiplatelet agent that acts in part as a phosphodiesterase inhibitor and as a competitive inhibitor of the platelet-derived growth factor (PDGF) receptor. Trapidil has been shown to attenuate intimal hyperplasia in rat and hamster models of balloon arterial injury and to inhibit restenosis after percutaneous transluminal coronary angioplasty in several small clinical trials. Monocyte chemoattractant protein-1 (MCP-1) is a PDGF-inducible monocyte chemoattractant that is thought to play a particularly important role in recruiting monocyte/macrophages to sites of atherosclerosis and vessel injury. We hypothesized that, because of its ability to antagonize PDGF-mediated events, trapidil would inhibit the synthesis of MCP-1 and decrease macrophage accumulation in the injured arterial wall. Hypercholesterolemic rabbits were treated with trapidil (60 mg/kg/day subcutaneously) the day before and then daily for 6 days after balloon injury of the femoral artery; control rabbits received vehicle only. Trapidil resulted in a 75% reduction in MCP-1 expression and macrophage accumulation in the arterial wall 7 days after injury. This study suggests that trapidil has potent anti-inflammatory properties and that its activity in attenuating intimal hyperplasia may be in part attributed to its effects on macrophage accumulation.
Poon
M
M
The Cardiovascular Institute, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
Cohen
J
J
Siddiqui
Z
Z
Fallon
J T
JT
Taubman
M B
MB
D000818:Animals; D002404:Catheterization / Q000009:adverse effects*; D002452:Cell Count / Q000187:drug effects; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005263:Femoral Artery / Q000293:injuries* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D014192:Trapidil / Q000494:pharmacology*; D014947:Wounds and Injuries / Q000378:metabolism* / Q000473:pathology*
D018932:Chemokine CCL2; D010975:Platelet Aggregation Inhibitors; D014192:Trapidil