Smooth Muscle Nitric Oxide Responsiveness and Clinical Maturation of Hemodialysis Arteriovenous Fistulae

Abstract

The arteriovenous fistula is the preferred type of hemodialysis vascular access for patients with end-stage renal disease, but a high proportion of newly created fistulas fail to mature for use. Stenosis caused by neointimal hyperplasia often is present in fistulas with maturation failure, suggesting that local mechanisms controlling vascular smooth muscle cell (SMC) migration and proliferation are important contributors to maturation failure. SMCs cultured from explants of vein tissue obtained at the time of fistula creation from 19 patients with end-stage renal disease were studied to determine whether smooth muscle responsiveness to nitric oxide is associated with fistula maturation outcomes. Nitric oxide-induced inhibition of smooth muscle cell migration, but not proliferation, was greater in cells from patients with subsequent fistula maturation success than from patients with subsequent fistula maturation failure (mean inhibition percentage, 17 versus 5.7, respectively; P = 0.035). Impaired nitric oxide responsiveness was associated with oxidation of the calcium regulatory protein, sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA), and was reversed by overexpressing SERCA (1.8-fold increase in inhibition, P = 0.0128) or down-regulating Nox4-based NADPH oxidase (2.3-fold increase in inhibition; P = 0.005). Our data suggest that the nitric oxide responsiveness of SMC migration is associated with fistula maturation success and raises the possibility that therapeutic restoration of nitric oxide responsiveness through manipulation of local mediators may prevent fistula maturation failure.

The effect of endothelial nitric oxide synthase on the hemodynamics and wall mechanics in murine arteriovenous fistulas

“…In the NO front, Tong et al . isolated SMCs from human vein samples used for creating AVFs in CKD patients and found that NO responsiveness of human venous SMCs in vitro was associated with AVF maturation in vivo 35 . Additionally, Geenen et al .…”

Antioxidant Properties of Curcumin and Its Impact on Arteriovenous Fistula Maturation in End-Stage Kidney Disease Patient with Diabetes Mellitus Type 2

“…However, several previous studies support this present study's indings. An increase of CD68 (a macrophage marker, an in lammation marker) and decreased antioxidant enzyme superoxide dismutase 1 (SOD 1) in the veins were signi icantly associated with maturation success (Tong et al, 2017). This previous study results suggest a decrease of oxidant state of the vein was associated with maturation success (Tong et al, 2017).…”

Comparing the vascular thromboembolic events following arteriovenous fistula in Chinese population with end-stage renal diseases receiving Clopidogrel versus Beraprost sodium therapy: a retrospective cohort study

“…There is a body of evidence suggesting that poor vascular elasticity and endovascular stenosis underlie a significant proportion of patients of VTEs [25, 26]. Endometrial damage following an AVF surgery can contribute to the occurrence of VTEs [25, 27].…”