Age-dependent impairment of reendothelialization after arterial injury -: Role of vascular endothelial growth factor
Age-dependent impairment of reendothelialization after arterial injury -: Role of vascular endothelial growth factor
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DOI：
10.1161/01.cir.0000050652.47145.4c
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发表时间：
2003-01-21
期刊：
影响因子：
37.8
通讯作者：
Rivard, A
中科院分区：
文献类型：
--
作者：
Gennaro, G;Ménard, C;Rivard, A
研究背景：高龄和动脉粥样硬化性疾病之间的联系机制尚不清楚。由于动脉粥样硬化的发展，局部内皮损伤的反应，我们调查了血管愈合和reendothelialization.Methods和Results-Endothelialdeudation老化的影响进行球囊血管成形术的髂动脉在年轻和老年新西兰白色兔。损伤后28天Evans蓝染色后的平面分析显示，与年轻动物相比，老年动物的再内皮化显著减少，这与老年兔新生内膜形成的重要增加有关。血管内皮生长因子（VEGF）在球囊损伤后迅速诱导。然而，动脉血管内皮生长因子的表达显着减少，在老年与年轻的动物。为了证实VEGF在再内皮化的年龄依赖性损伤中的作用，在髂动脉血管成形术时局部递送编码VEGF（165）的腺病毒载体（adeno-VEGF）。与对照载体（adeno-betaGal）治疗的动物相比，再内皮化显着改善和新生内膜形成减少在老年兔adeno-VEGF. Conclusions，这些结果首次记录动脉损伤后再内皮化的年龄依赖性损害。我们的研究表明，补充VEGF可能是一个有用的策略，以加速再内皮化和改善血管愈合的背景下，老化。
Background-The mechanisms responsible for the association between advanced age and atherosclerotic diseases are not clear. Because atherosclerosis develops in response to local endothelial injuries, we investigated the effect of aging on vascular healing and reendothelialization.Methods and Results-Endothelium denudation was performed by balloon angioplasty of the iliac arteries in young and old New Zealand White rabbits. Planimetric analysis after Evans Blue staining at 28 days after injury showed a significant decrease in reendothelialization in old versus young animals, which was associated with an important increase in neointimal formation in old rabbits. Vascular endothelial growth factor (VEGF) was rapidly induced after balloon injury. However, arterial VEGF expression was significantly reduced in old versus young animals. To confirm the role of VEGF in the age-dependent impairment of reendothelialization, an adenoviral vector encoding for VEGF(165) (adeno-VEGF) was locally delivered at the time of iliac artery angioplasty. Compared with animals treated with the control vector (adeno-betaGal), reendothelialization was significantly improved and neointimal formation reduced in old rabbits treated with adeno-VEGF.Conclusions-These results document for the first time an age-dependent impairment of reendothelialization after arterial injury. Our study indicates that VEGF supplementation may represent a useful strategy to accelerate reendothelialization and improve vascular healing in the context of aging.