Inhibitory effects of prostacyclin analogue, TFC-132, on aortic neointimal thickening in vivo and smooth muscle cell proliferation in vitro.
Effects of a new prostacyclin analogue, TFC-132, on neointimal thickening following intimal mechanical injury and on the proliferation of cultured aortic smooth muscle cells (SMCs) were studied. The intimal injury was induced by indwelling of polyethylene tubing for 24 h in the rabbit aorta. Rabbits were killed 10 days after drawing out the tubing. TFC-132 (0.6 mg/kg or 1.2 mg/kg) was given orally at 8-h intervals through the experiment. The serum concentrations of the analogue rose significantly 1 and 2 h after administration. The mean intimal thickening in the TFC-132 treated groups was significantly thinner than in the control one. Human aortic SMCs were cultured and 3H-thymidine incorporation into DNA (DNA synthesis) was measured at the varying concentrations of TFC-132. The analogue inhibited DNA synthesis of cultured SMCs at 10(-6) and 10(-5) M. These data indicate that a new prostacyclin analogue, TFC-132, has an inhibitory effect on the neointimal thickening after intimal injury and on the aortic SMC proliferation.
First Department of Pathology, Miyazaki Medical College, Japan.
Y
Y
Asada
A
A
Kisanuki
K
K
Hatakeyama
S
S
Takahama
T
T
Koyama
S
S
Kurozumi
A
A
Sumiyoshi
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D001161:Arteriosclerosis / Q000517:prevention & control; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011465:Prostaglandins, Synthetic / Q000097:blood / Q000494:pharmacology*; D011817:Rabbits; D013936:Thymidine / Q000378:metabolism
D011465:Prostaglandins, Synthetic; C091799:TFC 132; D004247:DNA; D011464:Epoprostenol; D013936:Thymidine