Transcriptomics of Human Arteriovenous Fistula Failure: Genes Associated With Nonmaturation
Transcriptomics of Human Arteriovenous Fistula Failure: Genes Associated With Nonmaturation
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DOI：
10.1053/j.ajkd.2018.12.035
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发表时间：
2019-07-01
影响因子：
13.2
通讯作者：
Vazquez-Padron, Roberto, I
中科院分区：
文献类型：
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作者：
Martinez, Laisel;Tabbara, Marwan;Vazquez-Padron, Roberto, I
原理与目的：改善动静脉内瘘（AVF）的结局需要更好地了解成熟或失败的生物学基础。我们目前的成熟知识依赖于从其他血管病理学的推断，这并不包括AVF重塑的独特方面。本研究比较了入路前（天然）静脉和AVF的RNA表达与不同的成熟outcomes.Study设计：病例对照研究。设置和参与者：64例患者接受2阶段AVF手术在一个单一的中心。使用RNA测序（RNA-seq）分析19个天然静脉和19个AVF样品。使用实时聚合酶链反应研究了58例自体静脉; 45例使用免疫组织化学; 19例使用Western印迹分析。预测因子：自体静脉和AVF中的RNA表达。结果：解剖不成熟，定义为AVF从未达到内径6 mm。分析方法：从接受2期AVF创建的患者中获得预通路自体静脉和AVF样本。使用RNA-seq分析在通路创建后随后成熟或失败的静脉，以寻找与成熟失败相关的基因。用实时聚合酶链反应、免疫组化和Western印迹分析证实了与未成熟相关的基因。此外，评估了入路前基因表达与术后形态之间的关联。结果：促炎基因（CSF 3R、FPR 1、S100 A8、S100 A9和VNN 2）在失败的预接入静脉中上调（假发现率< 0.05），并且它们的表达共定位于平滑肌细胞。S100 A8、S100 A9的表达与术后内膜增生、中膜纤维化和内膜增生产物相关（r = 0.32-0.38; P < 0.05）。AVF成熟或失败的转录相似的时间translocation.Limitations：小样本量，分析只有上臂静脉和transposed fistulas.Conclusions：增加前入路静脉中的促炎基因的表达似乎与更大的风险AVF不成熟。
Rationale & Objective: Improving arteriovenous fistula (AVF) outcomes requires better understanding of the biology underlying maturation or failure. Our current knowledge of maturation relies on extrapolation from other vascular pathologies, which does not incorporate unique aspects of AVF remodeling. This study compares the RNA expression of pre-access (native) veins and AVFs with distinct maturation outcomes.Study Design: Case-control study.Setting & Participants: 64 patients undergoing 2-stage AVF surgeries at a single center. 19 native veins and 19 AVF samples were analyzed using RNA sequencing (RNA-seq). 58 native veins were studied using real-time polymerase chain reaction; 45, using immunohistochemistry; and 19, using Western blot analysis.Predictor: RNA expression in native veins and AVFs.Outcome: Anatomic nonmaturation, defined as an AVF that never achieved an internal diameter 6 mm.Analytical Approach: Pre-access native veins and AVF samples were obtained from patients undergoing 2-stage AVF creation. Veins that subsequently matured or failed after access creation were analyzed using RNA-seq to search for genes associated with maturation failure. Genes associated with nonmaturation were confirmed using real-time polymerase chain reaction, immunohistochemistry, and Western blot analysis. In addition, the association between pre-access gene expression and postoperative morphology was evaluated. RNA-seq was also performed on AVFs to search for transcriptional differences between AVFs that matured and those that failed at the time of transposition.Results: Pro-inflammatory genes (CSF3R, FPR1, S100A8, S100A9, and VNN2) were upregulated in pre-access veins that failed (false discovery rate < 0.05), and their expression colocalized to smooth muscle cells. Expression of S100A8 and S100A9 correlated with postoperative intimal hyperplasia and the product of medial fibrosis and intimal hyperplasia (r = 0.32-0.38; P < 0.05). AVFs that matured or failed were transcriptionally similar at the time of transposition.Limitations: Small sample size, analysis of only upper-arm veins and transposed fistulas.Conclusions: Increased expression of proinflammatory genes in pre-access veins appears to be associated with greater risk for AVF nonmaturation.