DIFFERENCES IN GROWTH-FACTOR RESPONSE IN SMOOTH-MUSCLE CELLS ISOLATED FROM ADULT AND NEONATAL RAT ARTERIES

The development of atherosclerosis includes an abnormal proliferation of smooth muscle cells (SMCs) in the arterial intima. The factors responsible for this process remain to be identified, but earlier studies have suggested that age-related changes in growth-regulatory mechanisms may be involved. In the present study growth-regulatory mechanisms of neonatal and adult rat SMCs have been compared both in early passage and after subcultivation. Neonatal SMCs in early passage were found to have a high rate of spontaneous DNA synthesis and showed little response to stimulation with growth factors. Early passage adult SMCs showed a lower rate of spontaneous DNA synthesis but responded well to exogenous growth factors. There was no difference in the gene or surface expression of receptors for platelet-derived growth factor (PDGF) between neonatal and adult cells, and there was no significant difference in the amount of inositol phosphate formed in the cells after stimulation with PDGF BB. However, there was increased expression of PDGF A chain mRNA in serum-starved neonatal cells as compared to adult serum-starved SMCs. After subcultivation (seven to nine passages) neonatal SMCs started to become senescent, had a low rate of spontaneous DNA synthesis and were more sensitive to growth factor stimulation than in early passage. Adult SMCs did not demonstrate signs of senescence after subcultivation. The results demonstrate marked differences in the mechanisms regulating growth of neonatal and adult rat SMCs and suggest that the increased sensitivity of adult cells to exogenous growth factors and the inability of these cells to become senescent may be important factors in atherogenesis.