Vascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Cells. 2024 Oct 1;13(19):1637. doi: 10.3390/cells13191637.
Vascular access is an indispensable component of haemodialysis therapy for end-stage kidney disease patients. The arteriovenous fistula (AVF) is most common, but importantly, two-year failure rates are greater than fifty percent. AVF failure can occur due to a lack of suitable vascular remodelling, and inappropriate inflammation preventing maturation, or alternatively neointimal hyperplasia and vascular stenosis preventing long-term use. A comprehensive mechanistic understanding of these processes is still lacking, but recent studies highlight an essential role for inflammation from uraemia and the AVF itself. Inflammation affects each cell in the cascade of AVF failure, the endothelium, the infiltrating immune cells, and the vascular smooth muscle cells. This review examines the role of inflammation in each cell step by step and the influence on AVF failure. Inflammation resulting in AVF failure occurs initially via changes in endothelial cell activation, permeability, and vasoprotective chemokine secretion. Resultingly, immune cells can extravasate into the subendothelial space to release inflammatory cytokines and cause other deleterious changes to the microenvironment. Finally, all these changes modify vascular smooth muscle cell function, resulting in excessive and unchecked hyperplasia and proliferation, eventually leading to stenosis and the failure of the AVF. Finally, the emerging therapeutic options based off these findings are discussed, including mesenchymal stem cells, small-molecule inhibitors, and far-infrared therapies. Recent years have clearly demonstrated a vital role for inflammation in deciding the fate of the AVF, and future works must be centred on this to develop therapies for a hitherto unacceptably underserved patient population.
血管通路是终末期肾病患者血液透析治疗不可或缺的组成部分。动静脉瘘（AVF）最为常见，但重要的是，其两年失败率大于 50%。AVF 失败可能是由于缺乏合适的血管重塑，以及炎症预防成熟不当，或者是新生内膜过度增生和血管狭窄阻止长期使用。尽管人们对这些过程的全面机制理解仍然不足，但最近的研究强调了尿毒症和 AVF 本身引起的炎症的重要作用。炎症影响 AVF 失败级联反应中的每一个细胞，包括内皮细胞、浸润的免疫细胞和血管平滑肌细胞。本文逐步检查了炎症在每个细胞步骤中的作用及其对 AVF 失败的影响。导致 AVF 失败的炎症最初通过改变内皮细胞的激活、通透性和血管保护趋化因子的分泌而发生。由此，免疫细胞可以渗出到血管内皮细胞下腔室，释放炎症细胞因子，并对微环境造成其他有害变化。最后，所有这些变化都会改变血管平滑肌细胞的功能，导致过度和不受控制的增生和增殖，最终导致狭窄和 AVF 失败。最后，讨论了基于这些发现的新兴治疗选择，包括间充质干细胞、小分子抑制剂和远红外线治疗。近年来，炎症在决定 AVF 命运方面的重要作用已得到明确证实，未来的研究必须以此为中心，为迄今服务不足的患者群体开发治疗方法。
