VEGF gene transfer reduces intimal thickening via increased production of nitric oxide in carotid arteries
VEGF gene transfer reduces intimal thickening via increased production of nitric oxide in carotid arteries
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DOI：
10.1089/hum.1997.8.15-1737
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发表时间：
1997-10-10
影响因子：
4.2
通讯作者：
YlaHerttuala, S
中科院分区：
文献类型：
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作者：
Laitinen, M;Zachary, I;YlaHerttuala, S
动脉内膜增厚和平滑肌细胞（SMC）增殖仍然是血管手术和其他类型的血管操作后的主要问题，我们研究了内皮细胞（EC）特异性血管内皮生长因子（VEGF）使用插入颈动脉周围的硅胶项圈进行基因转移，作为引起内膜SMC生长的试剂和作为血管平滑肌细胞的储存器，该模型保持了EC的完整性，并允许直接血管外基因转移而无需任何血管内操作。与β-半乳糖苷酶（lacZ）转染的对照动脉相比，质粒/脂质体介导的VEGF基因转移显着减少内膜增厚1周后的基因转移。一氧化氮（NO）合酶抑制剂L-NAME可消除VEGF和lacZ转染动脉内膜增厚的差异。此外，VEGF可引起培养的人脐静脉EC释放NO。结论血管外VEGF基因转移可抑制内膜生长，并可用于预防血管手术中内膜增厚。我们的研究结果进一步表明，VEGF可能通过一种机制，涉及VEGF诱导的NO从内皮细胞的生产减少SMC增殖。
Thickening of the arterial intima and smooth muscle cell (SMC) proliferation remain major problems after vascular surgery and other types of vascular manipulations, We studied the effect of endothelial cell (EC)-specific vascular endothelial growth factor (VEGF) gene transfer on the thickening of the intima using a silicone collar inserted around carotid arteries that acted both as the agent that caused intimal SMC growth and as a reservoir for the transfected gene, The model preserved EC integrity and permitted direct extravascular gene transfer without any intravascular manipulation. Compared to beta-galactosidase (lacZ)-transfected control arteries, plasmid/liposome-mediated VEGF gene transfer significantly reduced intimal thickening 1 week after the gene transfer. Administration to the experimental animals of the nitric oxide (NO) synthase inhibitor L-NAME abolished the difference in intimal thickening between VEGF and lacZ-transfected arteries, Furthermore, VEGF caused NO release from cultured human umbilical vein EC, It is concluded that extravascular VEGF gene transfer attenuates intimal growth and could be useful for the prevention of intimal thickening during vascular surgery, Our results further suggest that VEGF may reduce SMC proliferation via a mechanism that involves VEGF-induced NO production from the endothelium.