Effect of estrogen on vascular smooth muscle cells is dependent upon cellular phenotype Original Research Article

To investigate the growth-regulating action of estrogen on vascular smooth muscle cells (SMC), effects of β-17-estradiol (β-E2) on phenotypic modulation and proliferation of rabbit aortic SMC were observed in vitro. At 10−8 M, β-E2 significantly slowed the decrease in volume fraction of myofilaments (Vv myo) of freshly dispersed SMCs in primary culture, indicating an inhibitory effect of β-E2 on spontaneous phenotypic modulation of SMC from a contractile to a synthetic phenotype. Freshly dispersed SMCs treated with β-E2 also had a relatively longer quiescent phase than control cells before intense proliferation occurred. This was in contrast to SMCs in passage 2–3 (synthetic state), where β-E2-treated cells replicated significantly faster than untreated cells. β-E2 also markedly enhanced the serum-induced DNA synthesis of synthetic SMCs in a concentration-dependent manner within physiological range (10−10 to 10−8 M). These findings indicate that the growth-regulating effect of estrogen on vascular SMC is dependent on the cellʹs phenotypic state. It delays the cell cycle re-entry of the contractile SMCs by retarding their phenotypic modulation; however, once cells have modulated to the synthetic phenotype, it promotes their replication.