Effect of TFC-612, a 7-thia prostaglandin E1 derivative, on intimal thickening after endothelial injury with balloon catheter in rats.
The effect of TFC-612, methyl-6-[(1R,2S,3R)-hydroxy-2-](1E,3S,5R)-3- hydroxy-5-methyl-1-nonenyl]-5-oxocyclopentyl)thio] hexanoate, on intimal thickening of carotid artery 14 days after endothelium denudation with a balloon catheter was examined in rats. This compound significantly suppressed the neointimal area and the ratio of intimal and medial layer by 41.1% and 31.4%, respectively, at 3.2 micrograms/rat/h s.c. infusion. At this dose, this compound did not inhibit platelet aggregation induced by either collagen or ADP. It did not inhibit bromodeoxyuridine incorporation into medial smooth muscle cells at 3 days after injury. In in vitro experiments, TFC-612 did not inhibit the [3H]thymidine uptake into cultured smooth muscle cells, but it showed significant inhibition of smooth muscle cell migration induced by platelet-derived growth factor (PDGF) at more than 10(-9) M. This compound increased cyclic AMP levels dose dependently in cultured smooth muscle cells at more than 10(-8) M. These results suggest that TFC-612 inhibits intimal thickening by inhibition of smooth muscle cell migration from media to intima through cyclic AMP elevation.
Motoyama
Y
Y
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Seki
J
J
Katoh
Y
Y
Nishio
M
M
Yoshida
K
K
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D020212:Carotid Artery Injuries; D017536:Carotid Artery, Common / Q000473:pathology; D002404:Catheterization; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013936:Thymidine / Q000378:metabolism; D017539:Tunica Intima / Q000187:drug effects* / Q000293:injuries / Q000473:pathology / Q000503:physiopathology
D010975:Platelet Aggregation Inhibitors; D010982:Platelet-Derived Growth Factor; C054546:TFC 612; D000527:Alprostadil; D001973:Bromodeoxyuridine; D013936:Thymidine