TROPOELASTIN GENE-EXPRESSION IN INDIVIDUAL VASCULAR SMOOTH-MUSCLE CELLS - RELATIONSHIP TO DNA-SYNTHESIS DURING VASCULAR DEVELOPMENT AND AFTER ARTERIAL INJURY

After vascular injury, quiescent adult smooth muscle cells (SMCs) reve rt to a more immature synthetic-state phenotype concomitant with the o nset of cell replication. The relationship between SMC proliferation a nd the reexpression of genes characteristic of immature SMCs (eg, trop oelastin [TE]), on an individual cell basis, has not been determined. Using a combined bromodeoxyuridine (BrdU) immunocytochemistry-TE in si tu hybridization technique, we determined the relationship between DNA synthesis and TE gene expression in the rat vascular wall during deve lopment and after experimental injury. During the early development of the aortic media (embryonic days 13 to 18), low but detectable levels of TE expression occurred equally in both replicating and nonreplicat ing SMCs. TE message levels dramatically increased in the late fetal a nd early postnatal periods (fetal day 19 to 1 month postpartum), after a precipitous drop in SMC replication, and then decreased to undetect able levels by postpartum day 60. After balloon catheter injury in the adult, a developmental sequence of SMC replication followed by TE gen e expression was reiterated in both the media and in the developing ne ointima. On an individual cell basis, adult SMCs replicating after inj ury expressed little or no TE message; detectable TE gene expression o ccurred only in nonreplicating SMCs. The most important implications o f these data are that (1) adult SMCs replicating after injury appear t o revert to a preelastogenic embryonic phenotype; (2) maximal TE expre ssion occurs in SMCs only after the cessation of cell replication; and (3) in both the media and the neointima, adult SMCs responding to inj ury undergo temporally sequential changes in phenotype reflective of S MC development.