Sarkar R, Dickinson C J, Stanley J C
Conrad Jobst Vascular Research Laboratories, Section of Vascular Surgery, Department of Surgery, Ann Arbor, Michigan, USA.
J Vasc Surg. 1999 Apr;29(4):685-93. doi: 10.1016/s0741-5214(99)70315-0.
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.
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.
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.
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.
生长抑素类似物在体内可抑制新生内膜增生和平滑肌细胞（SMC）增殖。将生长抑素基因转导入内皮细胞（EC）是向动脉损伤区域局部递送生长抑素的一种潜在方法。本研究检验了以下假设：将生长抑素逆转录病毒基因转导入EC可在体外抑制SMC增殖，并评估了生长抑素类似物对DNA合成及SMC生长的影响。
采用培养基转移和共培养法来确定产生生长抑素的EC对体外SMC增殖的影响。测定了多种生长抑素同工型和类似物对SMC增殖、血清再刺激的静止SMC的有丝分裂原作用以及动脉外植体的影响。
尽管EC产生了生物学相关浓度的生长抑素，但未观察到对SMC增殖的抑制作用。生长抑素类似物抑制动脉外植体中的DNA合成，但不抑制培养的SMC的DNA合成或生长，这表明生长抑素可能对SMC表型的初始转变有影响。
生长抑素仅在向增殖表型早期转变期间对SMC增殖发挥抑制作用。这种体内转变与培养的SMC的标准血清再刺激模型之间存在显著差异。这些差异可能解释了生长抑素在标准体外模型中未能抑制SMC增殖的原因。
