Dual modes of action of platelet-derived growth factor and its inhibition by trichostatin-A for DNA synthesis in primary cultured smooth muscle cells of rat aorta.

The effects of platelet-derived growth factor (PDGF) on the start and rate of DNA synthesis were investigated with or without (R)-trichostatin-A (TS-A) in primary cultured and synchronized smooth muscle cells (SMC) of rat aorta. After the SMC at the G0 phase were precultured with 10 and 100 ng/ml PDGF for 3 h and washed out,they were then stimulated with 3% fetal bovine serum (FBS). FBS-stimulated DNA synthesis was determined every 3 h for 24-30 h. The SMC pre-cultured with PDGF started DNA synthesis at an earlier time, dependent on the concentrations, suggesting an acceleration of competence. After the SMC were precultured with PDGF (30 ng/ml) plus TS-A (0.1, 0.3, 1.0 and 3.0 micrograms/ml) for 3 h and washed out, the SMC were then stimulated by 1% FBS. TS-A delayed the starting time of DNA synthesis in a concentration-dependent manner. During the prolonged culture with PDGF (1, 3, 10 and 100 ng/ml) and FBS (3%), the rate of DNA synthesis was more rapid than in cells pretreated with PDGF alone, suggesting an acceleration of progression. These results suggest that 1) PDGF stimulates DNA synthesis dually during the competence and progression phases, and 2) PDGF-induced competence is inhibited by TS-A in primary cultured SMC.