Effects of 1, 25-dihydroxyvitamin D 3 on the synthesis of DNA and glycosaminoglycans by rat aortic smooth muscle cells in vitro

Abstract

Studies were made on the effects of 1, 25-dihydroxyvitamin D 3 [1, 25-(OH) 2D 3] on the syntheses of DNA and glycosaminoglycans (GAG) by rat aortic smooth muscle cells (SMC) in vitro . DNA synthesis in cell cultures without fetal calf serum (FCS) was stimulated by incubation for 24 hr with 1, 25-(OH) 2D 3 at concentrations of more than 10 −12 M, stimulation being maximal at a concentration of 10 −8 M. On the other hand, GAG synthesis was inhibited dose-dependently by 1, 25-(OH) 2D 3 at concentrations of more than 10 −11 M. Other vitamin D 3 metabolites had similar, but weaker effects on the syntheses of DNA and GAG by SMC, which were proportional to their affinities for the 1, 25-(OH) 2D 3 receptor. These effects of 1, 25-(OH) 2D 3 were not seen after short-term incubation (1 hr). These findings suggested that 1, 25-(OH) 2D 3 stimulated the proliferation of SMC independent of growth factors in FCS, and that its effects were dependent on its specific receptor. Excess 1, 25-(OH) 2D 3 might cause arteriosclerosis not only by stimulating proliferation but also by suppressing GAG synthesis.