Liu Jia, Zhang Dingyao, Brahmandam Anand, Matsubara Yutaka, Gao Mingjie, Tian Jingru, Liu Bing, Shu Chang, Dardik Alan
Department of Vascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China.
The Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, CT, USA.
J Vasc Access. 2024 Jan;25(1):172-186. doi: 10.1177/11297298221102298. Epub 2022 Jun 10.
Arteriovenous fistulae (AVF) are the preferred access for hemodialysis but still have poor rates of maturation and patency limiting their clinical use. The underlying mechanisms of venous remodeling remain poorly understood, and only limited numbers of unbiased approaches have been reported.
Biological Gene Ontology (GO) term enrichment analysis and differentially expressed genes (DEG) analysis were performed for three AVF datasets. A microRNA enrichment analysis and L1000CDS query were performed to identify factors predicting AVF patency.
The inflammatory and immune responses were activated during both early and late phases of AVF maturation, with upregulation of neutrophil and leukocyte regulation, cytokine production, and cytokine-mediated signaling. In men with failed AVF, negative regulation of myeloid-leukocyte differentiation and regulation of macrophage activation were significantly upregulated. Compared to non-diabetic patients, diabetic patients had significantly reduced immune response-related enrichment such as cell activation in immune response, regulation of immune-effector process, and positive regulation of defense response; in addition, diabetic patients showed no enrichment of the immune response-regulating signaling pathway.
These data show coordinated, and differential regulation of genes associated with AVF maturation, and different patterns of several pathways are associated with sex differences in AVF failure. Inflammatory and immune responses are activated during AVF maturation and diabetes may impair AVF maturation by altering these responses. These findings suggest several novel molecular targets to improve sex specific AVF maturation.
动静脉内瘘（AVF）是血液透析的首选通路，但成熟率和通畅率仍然较低，限制了其临床应用。静脉重塑的潜在机制仍知之甚少，且仅有有限数量的无偏倚方法被报道。
对三个AVF数据集进行生物基因本体（GO）术语富集分析和差异表达基因（DEG）分析。进行微小RNA富集分析和L1000CDS查询以识别预测AVF通畅性的因素。
在AVF成熟的早期和晚期，炎症和免疫反应均被激活，中性粒细胞和白细胞调节、细胞因子产生以及细胞因子介导的信号传导上调。在AVF失败的男性中，髓系白细胞分化的负调节和巨噬细胞激活的调节显著上调。与非糖尿病患者相比，糖尿病患者的免疫反应相关富集显著减少，如免疫反应中的细胞激活、免疫效应过程的调节以及防御反应的正调节；此外，糖尿病患者未显示免疫反应调节信号通路的富集。
这些数据显示了与AVF成熟相关基因的协同和差异调节，并且几种通路的不同模式与AVF失败中的性别差异相关。AVF成熟过程中炎症和免疫反应被激活，糖尿病可能通过改变这些反应来损害AVF成熟。这些发现提示了几个改善性别特异性AVF成熟的新分子靶点。
