Effects of somatostatin, somatostatin analogs, and endothelial cell somatostatin gene transfer on smooth muscle cell proliferation in vitro.
OBJECTIVE
Somatostatin analogs inhibit neointimal hyperplasia and smooth muscle cell (SMC) proliferation in vivo. The gene transfer of somatostatin to endothelial cells (ECs) represents a potential means of local delivery of somatostatin to areas of arterial injury. This study tested the hypothesis that the retroviral gene transfer of somatostatin to ECs would inhibit SMC proliferation in vitro and evaluated the effects of somatostatin analogs on DNA synthesis and the growth of SMCs.


METHODS
Media transfer and coculture were used to determine the effects of somatostatin-producing ECs on SMC proliferation in vitro. The effects of a variety of somatostatin isoforms and analogs on the proliferation of SMCs, mitogenesis of serum-restimulated quiescent SMCs, and arterial explants were measured.


RESULTS
Despite the production of biologically relevant concentrations of somatostatin by ECs, no inhibition of SMC proliferation was noted. Somatostatin analogs inhibited DNA synthesis in arterial explants but did not inhibit either DNA synthesis or growth of cultured SMCs, which showed a likely effect of somatostatin on the initial transition in SMC phenotype.


CONCLUSIONS
Somatostatin exerts inhibitory effects on SMC proliferation only during the early transition to a proliferative phenotype. There are significant differences between this in vivo transition and the standard serum-restimulated model of cultured SMCs. These differences may account for the failure of somatostatin to inhibit SMC proliferation in the standard in vitro models.
Sarkar
R
R
Conrad Jobst Vascular Research Laboratories, Section of Vascular Surgery, Department of Surgery, Ann Arbor, Michigan, USA.
Dickinson
C J
CJ
Stanley
J C
JC
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004285:Dogs; D004730:Endothelium, Vascular / Q000166:cytology; D018014:Gene Transfer Techniques; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010641:Phenotype; D051381:Rats; D013004:Somatostatin / Q000031:analogs & derivatives / Q000235:genetics* / Q000494:pharmacology* / Q000502:physiology
D013004:Somatostatin; D004247:DNA