Inhibition of smooth muscle cell proliferation and migration in vitro by antisense oligonucleotide to c-myb.
Inhibition of smooth muscle cell proliferation and migration in vitro by antisense oligonucleotide to c-myb.
复制标题
c-myb 反义寡核苷酸体外抑制平滑肌细胞增殖和迁移。
DOI：
10.1016/s0741-5214(96)70240-9
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发表时间：
1996
影响因子：
4.3
通讯作者：
Graham,LM
中科院分区：
文献类型：
--
作者：
Pitsch,RJ;Goodman,GR;Minion,DJ;Madura2nd,JA;Fox,PL;Graham,LM
目的：平滑肌细胞的迁移和增殖是血管内膜增生的显著特征。以往的研究表明，抑制c-myb可抑制动脉SMC的增殖。我们的目的是评价针对c-myb的反义寡核苷酸对人造血管移植的SMC增殖和迁移的影响。方法用酶法从犬的主动脉和涤纶移植物中去除SMC。在增殖研究中，静止的SMC分别与μM反义寡核苷酸(GTGTCGGGGGGTCTCCGGGC)或正义寡核苷酸(GCCCGGAGACCCCGACAC)共同孵育。24小时后用[~3H]胸腺嘧啶核苷掺入法检测细胞增殖情况。结果c-myb反义寡核苷酸以剂量依赖的方式持续抑制自体和移植物SMCs的增殖和迁移。在10μM反义寡核苷酸浓度下，主动脉和移植物的增殖率分别为对照组的32%±20%和56%±9%。在25μM反义寡核苷酸作用下，移行的主动脉和移植物SMC的数量分别减少到对照组的41.9%±26.8%和51.9%±34.1%。结论c-myb反义寡核苷酸可能有助于抑制与内膜增生相关的SMC增殖和迁移。(《血管外科杂志》1996；23：783-91.)
PurposeSmooth muscle cell (SMC) migration and proliferation are prominent features of intimal hyperplasia. Previous studies have shown that inhibition of c- myb inhibits arterial SMC proliferation. Our goal was to evaluate the effect of an antisense oligonucleotide targeted to c- myb on the proliferation and migration of SMC explanted from synthetic vascular grafts.MethodsSMCs were enzymatically removed from aortas and Dacron grafts explanted from dogs (n = 5). For proliferation studies, quiescent SMCs were incubated with either 0.0, 0.5, 5.0, or 10.0 μM antisense (GTGTCGGGGTCTCCGGGC) or sense (GCCCGGAGACCCCGACAC) oligonucleotides to c- myb . Proliferation was measured after 24 hours by incorporation of [3H]thymidine. Migration was assessed 24 hours after a razor injury.ResultsAntisense to c- myb consistently inhibited proliferation and migration of both native aortic and graft SMCs in a dose-dependent fashion. At a concentration of 10 μM antisense oligonucleotide, aortic and graft SMC proliferation rates were 32% ± 20% and 56% ± 9% of control samples, respectively. At 25 μM antisense, the number of migrating aortic and graft SMCs decreased to 41.9% ± 26.8% and 51.9% ± 34.1% of control samples, respectively.ConclusionsOur results suggest that antisense oligonucleotides to c- myb may be useful in the inhibition of SMC proliferation and migration associated with development of intimal hyperplasia. (J Vasc Surg 1996;23:783-91.)