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 m uscle cell (SMC) proliferation in vivo. The gene transfer of somatostatin t o 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 o n 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 we re measured. Results: Despite the production of biologically relevant concentrations of somatostatin by ECs, no inhibition of SMC proliferation was noted. Somatost atin analogs inhibited DNA synthesis in arterial explants but did not inhib it either DNA synthesis or growth of cultured SMCs, which showed a likely e ffect of somatostatin on the initial transition in SMC phenotype. Conclusion: Somatostatin exerts inhibitory effects on SMC proliferation onl y during the early transition to a proliferative phenotype. There are signi ficant differences between this in vivo transition and the standard serum-r estimulated model of cultured SMCs. These differences may account for the f ailure of somatostatin to inhibit SMC proliferation in the standard in vitr o models.