Effects of beraprost sodium, a stable analogue of prostacyclin, on hyperplasia, hypertrophy and glycosaminoglycan synthesis of rat aortic smooth muscle cells.
The effects of beraprost sodium, a stable analogue of prostacyclin, on the syntheses of DNA, protein and glycosaminoglycans (GAG) of cultured vascular smooth muscle cells (SMC) were studied. SMC were isolated from the thoracic aorta of male Wistar rats. The syntheses of DNA, protein and GAG of SMC were determined by incorporations of [3H]thymidine, [3H]leucine and [35S]sulfuric acid, respectively. Insulin at a concentration of 10(-6) M stimulated DNA synthesis 4 fold compared to control. Beraprost sodium suppressed the insulin-stimulated DNA synthesis dose-dependently at concentrations greater than 10(-7) M and suppressed it by 68% at 10(-5) M. Platelet derived growth factor (PDGF) at a concentration of 20 ng/ml stimulated DNA synthesis 6 fold compared to control. Beraprost sodium suppressed the PDGF-stimulated DNA synthesis dose-dependently at concentrations greater than 10(-7) M and suppressed it by 51% at 10(-5) M. Beraprost sodium suppressed GAG synthesis dose-dependently at concentrations greater than 10(-7) M and suppressed it by 49% at 10(-5) M. However, beraprost sodium at concentrations up to 10(-5) M did not affect protein synthesis. These results indicate that beraprost sodium suppressed the proliferation and GAG synthesis of SMC but did not affect hypertrophy. Beraprost sodium may be a potent antiarteriosclerotic agent through suppression of hyperplasia of SMC and modification of matrix protein.
Koh
E
E
Department of Geriatric Medicine, Osaka University Medical School, Japan.
Morimoto
S
S
Jiang
B
B
Inoue
T
T
Nabata
T
T
Kitano
S
S
Yasuda
O
O
Fukuo
K
K
Ogihara
T
T
D000818:Animals; D001013:Aorta, Thoracic; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006131:Growth Inhibitors / Q000494:pharmacology; D006965:Hyperplasia; D006984:Hypertrophy; D007328:Insulin / Q000494:pharmacology; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D006025:Glycosaminoglycans; D006131:Growth Inhibitors; D007328:Insulin; D009124:Muscle Proteins; D010982:Platelet-Derived Growth Factor; C048081:beraprost; D004247:DNA; D011464:Epoprostenol