PDF(Pubmed)
Abstract：
Clinical outcomes of arteriovenous fistulae (AVF) for hemodialysis remain inadequate since biological mechanisms of AVF maturation and failure are still poorly understood. Aortocaval fistula creation (AVF group) or a sham operation (sham group) was performed in C57BL/6 mice. Venous limbs were collected on postoperative day 7 and total RNA was extracted for high throughput RNA sequencing and bioinformatic analysis. Genes in metabolic pathways were significantly downregulated in the AVF, whereas significant sex differences were not detected. Since gene expression patterns among the AVF group were heterogenous, the AVF group was divided into a \'normal\' AVF (nAVF) group and an \'outliers\' (OUT) group. The gene expression patterns of the nAVF and OUT groups were consistent with previously published data showing venous adaptive remodeling, whereas enrichment analyses showed significant upregulation of metabolism, inflammation and coagulation in the OUT group compared to the nAVF group, suggesting the heterogeneity during venous remodeling reflects early gene expression changes that may correlate with AVF maturation or failure. Early detection of these processes may be a translational strategy to predict fistula failure and reduce patient morbidity.
摘要：
动静脉瘘（AVF）用于血液透析的临床结果仍然不足，因为对AVF成熟和失败的生物学机制仍然知之甚少。在C57BL/6小鼠中进行主动脉瘘创建（AVF组）或假手术（假手术组）。术后第7天采集静脉肢体，提取总RNA进行高通量RNA测序和生物信息学分析。代谢途径中的基因在AVF中显著下调，而没有检测到显著的性别差异。由于AVF组中的基因表达模式是异质的，将AVF组分为“正常”AVF（nAVF）组和“异常值”（OUT）组。nAVF和OUT组的基因表达模式与先前发表的显示静脉适应性重塑的数据一致，而富集分析显示代谢显著上调，与nAVF组相比，OUT组的炎症和凝血功能，提示静脉重构过程中的异质性反映了可能与AVF成熟或衰竭相关的早期基因表达变化.这些过程的早期检测可能是预测瘘管失败和降低患者发病率的转化策略。
