Oxidative stress: An essential factor in the process of arteriovenous fistula failure

Abstract

For more than half a century, arteriovenous fistula (AVFs) has been recognized as a lifeline for patients requiring hemodialysis (HD). With its higher long-term patency rate and lower probability of complications, AVF is strongly recommended by guidelines in different areas as the first choice for vascular access for HD patients, and its proportion of application is gradually increasing. Despite technological improvements and advances in the standards of postoperative care, many deficiencies are still encountered in the use of AVF related to its high incidence of failure due to unsuccessful maturation to adequately support HD and the development of neointimal hyperplasia (NIH), which narrows the AVF lumen. AVF failure is linked to the activation and migration of vascular cells and the remodeling of the extracellular matrix, where complex interactions between cytokines, adhesion molecules, and inflammatory mediators lead to poor adaptive remodeling. Oxidative stress also plays a vital role in AVF failure, and a growing amount of data suggest a link between AVF failure and oxidative stress. In this review, we summarize the present understanding of the pathophysiology of AVF failure. Furthermore, we focus on the relation between oxidative stress and AVF dysfunction. Finally, we discuss potential therapies for addressing AVF failure based on targeting oxidative stress.

Anti-Fibrotic Potential of Angiotensin (1-7) in Hemodynamically Overloaded Rat Heart

“…Oxidative stress plays an important role in heart failure, including ACF. The increased synthesis and secretion of ROS leads to a disturbance of the oxidative balance, which in turn stimulates many signaling pathways that regulate various processes, including the promotion of cell proliferation and migration and the secretion of ECM [ 19 ]. The levels of TBARS, as a marker of oxidative stress, decreased in the left ventricle in the TGR(A1-7)3292 group compared to the HSD ACF group and in the right ventricle, and also in the TGR(A1-7)3292 group, but compared to the TGR ACF group ( Figure 2 ).…”

Sex Differences in Arteriovenous Fistula Failure: Insights from Bioinformatics Analysis

“…In addition, AGEs bind to RAGE and induce reactive oxygen species (ROS) production through activation of NADPH oxidase and NF-κB signaling pathways. Reactive oxygen species (ROS) have been shown to cause smooth muscle proliferation and intimal hyperplasia [ 10 , 59 ]. Therefore, blocking the AGE-RAGE signaling pathway may have great potential significance for the treatment of AVF failure.…”

“…Although these factors show considerable differences between different regions and populations, an increasing number of basic studies have revealed common molecular mechanisms that mediate AVF failure [ 9 ]. Invasive intimal hyperplasia is the most important cause of AVF failure and is histologically characterized by constriction of the lumen and function of the outflow tract caused by the accumulation of large numbers of contractile smooth muscle cells, fibroblasts, immune cells, and extracellular matrix [ 1 , 10 , 11 ]. The occurrence of intimal hyperplasia is closely related to biological pathways such as inflammation, hypoxia, oxidative stress, and shear stress [ 12 ].…”

The rodent models of arteriovenous fistula

“…Patients with complications and treatment related to vascular access account for nearly one-third of HD admissions ( 2 ). One main reason for AVF maturation failure is insufficient outward remodeling, which fails to adapt to changes in hemodynamics following arterialization ( 7 ). Another reason is excessive neointimal hyperplasia (NIH) within the fistula and thrombosis at the anastomosis, leading to luminal stenosis ( 8 ).…”

“…An establishment of a good animal model to reproduce this particular pathophysiology is key to the rigour and success of subsequent studies. It was shown that multiple vascular biological pathways may be involved in causing the development of this pathologic change, including inflammation, oxidative stress, hypoxia, and altered hemodynamics ( 7 ). Large animals are anatomically and physically closer to human and can effectively demonstrate hemodynamic changes, which is a limitation of small animals.…”