Effects of somatostatin, somatostatin analogs, and endothelial cell somatostatin gene transfer on smooth muscle cell proliferation in vitro.
Effects of somatostatin, somatostatin analogs, and endothelial cell somatostatin gene transfer on smooth muscle cell proliferation in vitro.
复制标题
生长抑素、生长抑素类似物和内皮细胞生长抑素基因转移对体外平滑肌细胞增殖的影响。
DOI：
10.1016/s0741-5214(99)70315-0
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发表时间：
1999
影响因子：
4.3
通讯作者：
Stanley,JC
中科院分区：
文献类型：
--
作者：
Sarkar,R;Dickinson,CJ;Stanley,JC
目的抑瘤素类似物抑制体内新生内膜增生和平滑肌细胞（SMC）增殖。生长抑素基因转移到内皮细胞（ECs）代表了一种将生长抑素局部递送到动脉损伤区域的潜在手段。本研究验证了体外将生长抑素逆转录病毒基因转移至内皮细胞可抑制SMC增殖的假设，并评估了生长抑素类似物对DNA合成和SMCs生长的影响。方法采用培养基转移和共培养的方法，观察产生生长抑素的内皮细胞对体外SMC增殖的影响。测定了多种生长抑素同种异构体和类似物对SMCs增殖、血清刺激的静止SMCs有丝分裂和动脉外植体的影响。结果尽管ECs产生了生物学上相关浓度的生长抑素，但没有发现SMC增殖受到抑制。生长抑素类似物抑制动脉外植体的DNA合成，但不抑制培养SMC的DNA合成和生长，这可能表明生长抑素对SMC表型的初始转变有影响。结论生长抑素仅在SMC向增生表型转变早期对其增殖有抑制作用。这种体内转化与培养的SMCs的标准血清再刺激模型有显著差异。这些差异可能解释了生长抑素在标准体外模型中抑制SMC增殖的失败。（中华外科杂志1999；29:685-93。）
ObjectiveSomatostatin 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.MethodsMedia 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.ResultsDespite 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.ConclusionSomatostatin 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. (J Vasc Surg 1999;29:685-93.)