DNA aptamer raised against advanced glycation end products inhibits neointimal hyperplasia in balloon-injured rat carotid arteries
DNA aptamer raised against advanced glycation end products inhibits neointimal hyperplasia in balloon-injured rat carotid arteries
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DOI：
10.1016/j.ijcard.2013.12.143
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发表时间：
2014-02-15
影响因子：
3.5
通讯作者：
Yamagishi, Sho-ichi
中科院分区：
文献类型：
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作者：
Ojima, Ayako;Oda, Eriko;Yamagishi, Sho-ichi
背景：晚期糖基化终产物（AGE）及其受体（RAGE）相互作用在动脉中引起炎症和增殖反应，从而在心血管疾病中发挥作用。我们最近发现，针对AGE的高亲和力DNA适体（AGE-aptamer）通过阻断AGE在肾脏中的有害作用来阻止实验性糖尿病肾病的进展。然而，age适体对血管损伤的影响尚不清楚。在这项研究中，我们研究了age -适体是否以及如何抑制球囊损伤大鼠颈动脉内膜增生。方法：用戊巴比妥钠麻醉11周龄体重400 g的雄性Wistar大鼠。通过股动脉插入2F Fogaty导管，球囊损伤左颈总动脉3次。然后用微型渗透泵连续腹腔注射age -适体或对照适体（3 μ g/d） 2周。术后14天，切除左侧颈总动脉进行形态学、免疫组化和western blot分析。结果：与对照适体相比，AGE适体显著抑制球囊损伤后颈动脉新生内膜形成，降低球囊损伤后颈动脉AGE积累、氧化应激生成、增殖细胞核抗原阳性面积、巨噬细胞浸润、RAGE和血小板衍生生长因子- bb （PDGF-BB）表达水平。结论：age -适体通过抑制age - rage介导的氧化应激生成，减少PDGF-BB和巨噬细胞浸润，从而预防球囊损伤诱导的新生内膜增生。age适体可能是抑制球囊血管成形术后新内膜形成的一种新的治疗策略。2014爱思唯尔爱尔兰有限公司版权所有。
Background: Advanced glycation end products (AGE) and their receptor (RAGE) interaction elicit inflammatory and proliferative reactions in arteries, thus playing a role in cardiovascular disease. We have recently found that high-affinity DNA aptamer directed against AGE (AGE-aptamer) prevents the progression of experimental diabetic nephropathy by blocking the harmful actions of AGEs in the kidney. However, effects of AGE-aptamer on vascular injury remain unknown. In this study, we examined whether and how AGE-aptamer inhibits neointimal hyperplasia in balloon-injured rat carotid arteries.Methods: Male Wistar rats (weighting ca. 400 g at 11 weeks old) were anesthetized with sodium pentobarbital. The left common carotid artery was balloon-injured 3 times with 2F Fogaty catheter inserted through the femoral artery. Then the rats received continuous intraperitoneal infusion (3 mu g/day) of either AGE-aptamer or control-aptamer by an osmotic mini pump for 2 weeks. 14 days after the procedure, the left common carotid arteries were excised for morphometric, immunohistochemical and western blot analyses.Results: Compared with control-aptamer, AGE-aptamer significantly suppressed neointima formation after balloon injury and reduced AGE accumulation, oxidative stress generation, proliferation cell nuclear antigen-positive area, macrophage infiltration, RAGE and platelet-derived growth factor-BB (PDGF-BB) expression levels in balloon-injured carotid arteries.Conclusion: The present study suggests that AGE-aptamer could prevent balloon injury-induced neointimal hyperplasia by reducing PDGF-BB and macrophage infiltration via suppression of the AGE-RAGE-mediated oxidative stress generation. AGE-aptamer might be a novel therapeutic strategy for suppressing neointima formation after balloon angioplasty. (C) 2014 Elsevier Ireland Ltd. All rights reserved.