Rai Vikrant, Agrawal Devendra K
Department of Translational Research, Western University of Health Sciences, Pomona, CA 91766, USA.
Biomedicines. 2022 Feb 13;10(2):433. doi: 10.3390/biomedicines10020433.
Arteriovenous fistula (AVF) is vascular access created for hemodialysis in end-stage renal disease patients. AVF creation causes increased blood flow in the outflow vein with increased pressure. Increased blood flow, blood volume, and shear stress causes outward remodeling so that the outflow vein can withstand the increased pressure. Outward remodeling of the vein involved in AVF is necessary for AVF maturation, however, inward remodeling due to excessive neointimal hyperplasia (NIH) and chronic inflammation may end up with vessel thrombosis and AVF maturation failure. Early thrombosis of the vessel may be due to the luminal factors including NIH and chronic inflammation or due to chronic inflammation of the adventitial due to perivascular cuffing. Inflammation may either be due to an immune response to the vascular injury during AVF creation or injury to the surrounding muscles and fascia. Several studies have discussed the role of inflammation in vascular thrombosis due to intimal injury during AVF creation, but there is limited information on the role of inflammation due to surrounding factors like a muscle injury. The concept of perivascular cuffing has been reported in the nervous system, but there is no study of perivascular cuffing in AVF early thrombosis. We performed the bulk RNA sequencing of the femoral arterial tissue and contralateral arteries as we found thrombosed arteries after AVF creation. RNA sequencing revealed several significantly differentially expressed genes (DEGs) related to chronic inflammation and perivascular cuffing, including tripartite motif-containing protein 55 (TRIM55). Additionally, DEGs like myoblast determination protein 1 (MYOD1) increased after muscle injury and relates to skeletal muscle differentiation, and network analysis revealed regulation of various genes regulating inflammation via MYOD1. The findings of this study revealed multiple genes with increased expression in the AVF femoral artery and may provide potential therapeutic targets or biomarkers of early thrombosis in AVF maturation failure. Thus, not only the luminal factors but also the surrounding factors mediating vascular cuffing contribute to vessel thrombosis and AVF failure via early thrombosis, and targeting the key regulatory factors may have therapeutic potential.
动静脉内瘘（AVF）是为终末期肾病患者进行血液透析而建立的血管通路。AVF的建立会使流出静脉中的血流增加，压力升高。血流增加、血容量增加和剪切应力会导致向外重塑，使流出静脉能够承受升高的压力。AVF中涉及的静脉向外重塑对于AVF成熟是必要的，然而，由于过度的新生内膜增生（NIH）和慢性炎症导致的向内重塑最终可能导致血管血栓形成和AVF成熟失败。血管早期血栓形成可能是由于包括NIH和慢性炎症在内的管腔因素，也可能是由于血管周围袖套导致的外膜慢性炎症。炎症可能是由于对AVF建立过程中血管损伤的免疫反应，也可能是由于对周围肌肉和筋膜的损伤。几项研究讨论了炎症在AVF建立过程中内膜损伤导致的血管血栓形成中的作用，但关于肌肉损伤等周围因素导致的炎症作用的信息有限。血管周围袖套的概念已在神经系统中报道，但尚无关于AVF早期血栓形成中血管周围袖套的研究。在发现AVF建立后出现血栓形成的动脉后，我们对股动脉组织和对侧动脉进行了大量RNA测序。RNA测序揭示了几个与慢性炎症和血管周围袖套相关的显著差异表达基因（DEG），包括含三联体基序蛋白55（TRIM55）。此外，成肌细胞决定蛋白1（MYOD1）等DEG在肌肉损伤后增加，与骨骼肌分化有关，网络分析揭示了通过MYOD1对调节炎症的各种基因的调控。本研究结果揭示了在AVF股动脉中表达增加的多个基因，并可能为AVF成熟失败早期血栓形成提供潜在的治疗靶点或生物标志物。因此，不仅管腔因素，而且介导血管袖套形成的周围因素也通过早期血栓形成导致血管血栓形成和AVF失败，靶向关键调节因子可能具有治疗潜力。
