MicroRNA-155 promotes neointimal hyperplasia through smooth muscle-like cell-derived RANTES in arteriovenous fistulas.

MicroRNA-155 promotes neointimal hyperplasia through smooth muscle-like cell-derived RANTES in arteriovenous fistulas.
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MicroRNA-155 通过动静脉瘘中平滑肌样细胞衍生的 RANTES 促进新内膜增生。

DOI:
10.1016/j.jvs.2017.02.046
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发表时间:
2018-03
期刊:
J Vasc Surg
影响因子:
--
通讯作者:
JiahongXia
JiahongXia
中科院分区:
其他
文献类型:
--
作者:
JiahongXia

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动静脉内瘘(AVF)由于外塑不足和静脉新生内膜增生形成而导致大量失败。目的是研究AVF流出静脉中microRNA-155(miR-155)的确切调控机制。方法在C57 BL/6和miR-155−/−小鼠中以端对端的方式在颈静脉分支和颈动脉之间建立AVF,并以C57 BL/6为背景。在第7、14、21和28天收获静脉段,并使用实时定量聚合酶链反应在信使RNA水平对AVF进行组织学分析。AVF的流出静脉和正常大隐静脉,收集自慢性肾脏疾病和冠状动脉搭桥手术患者,通过组织学和分子生物学方法进行分析。结果静脉新生内膜增生在miR-155−/−小鼠中显著减轻,并且血管壁中几种趋化因子和细胞因子的表达,包括活化调节,正常T细胞表达和分泌因子(RANTES)、单核细胞趋化蛋白1和血管内皮生长因子被抑制。结论miR-155通过自分泌和旁分泌RANTES促进血管新生内膜的形成,在AVF的整个过程中,尤其是在晚期阶段,miR-155以核因子κ B依赖的方式促进血管新生内膜的形成。
ObjectiveArteriovenous fistula (AVF) suffers from a high number of failures caused by insufficient outward remodeling and venous neointimal hyperplasia formation. The aim was to investigate the exact mechanism by which microRNA-155 (miR-155) in the outflow vein of AVF is regulated.MethodsAVFs between the branch of the jugular vein and carotid artery in an end-to-end manner were created in C57BL/6 and miR-155−/−mice with a C57BL/6 background. The venous segments were harvested at day 7, 14, 21, and 28, and the AVFs were analyzed histologically and at a messenger RNA level using real-time quantitative polymerase chain reactions. The outflow vein of AVF and the normal great saphenous vein, collected from patients with chronic kidney disease and coronary artery bypass surgery, were analyzed by histologic and molecular biologic approaches.ResultsVenous neointimal hyperplasia is significantly alleviated in miR-155−/−mice, and the expression of several chemokines and cytokines in the vessel wall, including regulated on activation, normal T-cell expressed and secreted factor (RANTES), monocyte chemoattractant protein 1, and vascular endothelial growth factor, was inhibited. miR-155 promoted the RANTES expression of smooth muscle-like cells, which in turn facilitated cell proliferation and extracellular matrix production.ConclusionsmiR-155 enhances venous neointima formation through the autocrine and paracrine effects of smooth muscle-like cell-derived RANTES in a nuclear factor κB-dependent manner during the entire AVF process, especially at the advanced stage.
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