Prothrombotic effect of Rofecoxib in a murine venous thrombosis model.
The potential prothrombotic effect of the cyclooxygenase-2 (COX-2) inhibitor Rofecoxib (Vioxx) was investigated using murine thrombosis models. In a jugular vein thrombosis model (photochemically induced injury) in lean wild-type mice, Rofecoxib treatment for 4 weeks induced a mild prothrombotic tendency, as indicated by a shorter occlusion time as compared to placebo (median of 12 min versus 36 min; p < 0.05). Thrombus size was somewhat, but not significantly, enhanced after Rofecoxib treatment. In a femoral artery thrombosis model (FeCl3 induced injury) Rofecoxib did not cause an enhanced thrombotic tendency in mice with nutritionally induced or genetically determined (ob/ob) obesity. The occlusion time was comparable for obese wild-type mice with (8.8+/-0.7 min) or without (7.8+/-2.1 min) Rofecoxib treatment, as well as for ob/ob mice (8.5+/-0.7 min versus 6.8+/-3.0 min). Thus, an enhanced prothrombotic effect of Rofecoxib was detected when using a venous thrombosis model in lean mice, but not when using an arterial thrombosis model in obese mice.
Nagai
Nobuo
N
Center for Molecular and Vascular Biology, K.U. Leuven, Leuven, Belgium.
Hoylaerts
Marc F
MF
Gallacher
David J
DJ
Lu
Hua Rong
HR
Lijnen
H Roger
HR
D000818:Animals; D052246:Cyclooxygenase 2 Inhibitors / Q000633:toxicity*; D004195:Disease Models, Animal; D005263:Femoral Artery; D007601:Jugular Veins; D007783:Lactones / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D009765:Obesity / Q000097:blood / Q000150:complications; D010974:Platelet Aggregation / Q000187:drug effects; D013450:Sulfones / Q000633:toxicity*; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced / Q000209:etiology; D020246:Venous Thrombosis / Q000097:blood / Q000139:chemically induced* / Q000209:etiology
D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib