Cl. Cook et al., DEVELOPMENTALLY TIMED EXPRESSION OF AN EMBRYONIC GROWTH PHENOTYPE IN VASCULAR SMOOTH-MUSCLE CELLS, Circulation research, 74(2), 1994, pp. 189-196
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.