VEGF-A, VEGF-D and VEGF-DΔNΔC induced intimal hyperplasia in carotid arteries
VEGF-A, VEGF-D and VEGF-DΔNΔC induced intimal hyperplasia in carotid arteries
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DOI：
10.1111/j.1365-2362.2005.01555.x
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发表时间：
2005-11-01
影响因子：
5.5
通讯作者：
Ylä-Herttuala, S
中科院分区：
文献类型：
--
作者：
Bhardwaj, S;Roy, H;Ylä-Herttuala, S
背景 血管内皮生长因子（VEGF）在内膜增生和动脉粥样硬化形成中的作用仍不清楚。多项研究表明 VEGF 家族的一些成员可减少内膜增生，但其他研究则提出 VEGF 会加速再狭窄和动脉粥样硬化。本研究利用编码不同VEGF的腺病毒在家兔颈动脉项圈内膜增生模型中进行对比研究，以分析VEGF在内膜增生形成中的作用。 材料与方法采用硅橡胶项圈在饲喂胆固醇的新西兰白兔颈动脉中诱导内膜增生。使用项圈作为基因递送装置将编码 VEGF-A、VEGF-B、VEGF-C、VEGF-C-Delta N Delta C、VEGF-D 和 VEGF-D-Delta N Delta C 的腺病毒载体递送至外膜。以Adeno-LacZ为对照。结果 转染VEGF-A、VEGF-D和VEGF-D-Delta N Delta C的动脉内膜/中膜比例显着增加（P < 0.01）。VEGF-A、VEGF-D和VEGF-D-Delta N的外膜、中膜和内膜增殖细胞数量显着增加。 Delta C 转导动脉。这些动脉中的大多数内侧平滑肌细胞具有合成表型。 VEGF-A、VEGF-D 和 VEGF-D-Delta N Delta C 转导动脉中基质金属蛋白酶 2 (MMP-2) 和 MMP-9 的存在显着增加。外膜血管生成与内膜增生之间存在显着的正相关性。 结论 外膜递送编码VEGF-A、VEGF-D和VEGF-D-Delta N Delta C的腺病毒可增加兔项圈模型中的内膜增生。外膜血管生成与内膜增生呈正相关。这些结果表明，VEGF-A、VEGF-D和VEGF-D-Delta N Delta C的外膜有效产生可引起兔动脉内层增厚。
Background The role of vascular endothelial growth factors (VEGFs) in intimal hyperplasia and atherogenesis remains unknown. Several studies have suggested that some members of the VEGF family reduce intimal hyperplasia, but others have proposed that VEGFs accelerate restenosis and atherosclerosis. This investigation conducted a comparative study with adenoviruses encoding different VEGFs in a rabbit carotid artery collar model of intimal hyperplasia in order to analyze the role of VEGFs in the formation of intimal hyperplasia.Materials and methods Intimal hyperplasia was induced in the carotid arteries of cholesterol fed New Zealand White rabbits using a silastic collar. Adenoviral vectors encoding VEGF-A, VEGF-B, VEGF-C, VEGF-C-Delta N Delta C, VEGF-D and VEGF-D-Delta N Delta C were delivered to the adventitia using the collar as a gene delivery device. Adeno-LacZ was used as a control.Results A significant (P < 0.01) increase in the intima/media ratio was observed in the arteries transduced with VEGF-A, VEGF-D and VEGF-D-Delta N Delta C. There was a significant increase in the number of proliferating cells in the adventitia, media and intima of the VEGF-A, VEGF-D and the VEGF-D-Delta N Delta C transduced arteries. The majority of medial smooth muscle cells in these arteries had a synthetic phenotype. The presence of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the VEGF-A, VEGF-D and the VEGF-D-Delta N Delta C transduced arteries was significantly increased. A significant positive correlation was observed between adventitial angiogenesis and intimal hyperplasia.Conclusions Adventitial delivery of adenoviruses encoding VEGF-A, VEGF-D and VEGF-D-Delta N Delta C increased intimal hyperplasia in the rabbit collar model. Adventitial angiogenesis correlated positively with the intimal hyperplasia. These results indicated that efficient adventitial production of VEGF-A, VEGF-D and VEGF-D-Delta N Delta C can cause thickening of the inner layer of the artery in rabbits.