Modulations of elastin expression and cell proliferation by retinoids in cultured vascular smooth muscle cells

Effects of retinoid derivatives (retinol, retinal, retinoic acid, and etretinate) on elastin expression and cell proliferation in chick embryonic vascular smooth muscle cells were compared. Retinoic acid and etretinate inhibited cell proliferation to a greater extent than retinol and retinal. Retinol showed no significant effect on cell proliferation or elastin synthesis. Retinoic acid exhibited the most pronounced stimulatory effect on elastin synthesis with a maximum stimulation of 2.8-fold at the concentration of 10(-6) M for 24-48 h treatment. A comparable increase in elastin mRNA level was observed in the case of retinoic acid treatment. When the cells were serially passaged to the third subcultivation, elastin synthesis declined with increasing number of cell passages. Retinoic acid reversed this decline of elastin synthesis. The results indicate that retinoic acid was potentially active and retinol was inactive for both inhibition of cell proliferation and stimulation of elastin synthesis. The inhibitory activities of the four compounds for cell proliferation appear to parallel the stimulatory activities for elastin synthesis. The stimulation of elastin expression by retinoids may thus be closely related to the inhibition of cell proliferation.