DEVELOPMENTALLY TIMED EXPRESSION OF AN EMBRYONIC GROWTH PHENOTYPE IN VASCULAR SMOOTH-MUSCLE CELLS

Little is known about the phenotypic changes that occur in vascular sm ooth muscle cells (SMCs) as the developing aorta undergoes the transit ion from a loosely organized, highly replicative tissue to a morpholog ically mature, quiescent tissue. In the present study, we have charact erized the in vivo pattern of SMC replication during intrauterine and neonatal aortic development in the rat and have cultured and assessed the in vitro growth properties of embryonic, fetal, and neonatal vascu lar SMCs. Embryonic SMCs, which exhibited a very high in vivo replicat ion rate (75% to 80% per day), demonstrated a significant potential fo r self-driven replication, as assessed by the ability to proliferate u nder serum-deprived conditions. Several lines of evidence suggest that the autonomous growth of SMCs in the ''embryonic growth phenotype'' m ay be driven by a unique mechanism independent of known adult SMC mito gens: embryonic SMC replication was not associated with the detectable secretion of mitogenic activity capable of stimulating adult SMCs, an d embryonic SMCs were mitogenically unresponsive to a variety of known adult SMC growth factors. The capacity for self-driven growth was los t by embryonic day 20, suggesting that important changes in gene expre ssion and phenotype occur in developing SMCs between embryonic days 18 and 20. Taken together, the data describe a unique embryonic growth p henotype of vascular SMCs and suggest that the replication of aortic S MCs during intrauterine development is self driven, self regulated, an d controlled by a developmental timing mechanism. The conversion of SM Cs from the embryonic to the late fetal/adult growth phenotype will li kely be found to be an important component of a developmental system c ontrolling vascular morphogenesis.