Abstract
Creation of a hemodialysis arteriovenous fistula (AVF) causes aberrant vascular mechanics at and near the AVF anastomosis. When inadequately regulated, these aberrant mechanical factors may impede AVF lumen expansion to cause AVF maturation failure, a significant clinical problem with no effective treatments. The endothelial nitric oxide synthase (NOS3) system is crucial for vascular health and function, but its effect on AVF maturation has not been fully characterized. We hypothesize that NOS3 promotes AVF maturation by regulating local vascular mechanics following AVF creation. Here we report the first MRI-based fluid-structure interaction (FSI) study in a murine AVF model using three mouse strains: NOS3 overexpression (NOS3 OE) and knockout (NOS3−/−) on C57BL/6 background, with C57BL/6 as the wild-type control (NOS3+/+). When compared to NOS3+/+ and NOS3−/−, AVFs in the OE mice had larger lumen area. AVFs in the OE mice also had smoother blood flow streamlines, as well as lower blood shear stress at the wall, blood vorticity, inner wall circumferential stretch, and radial wall thinning at the anastomosis. Our results demonstrate that overexpression of NOS3 resulted in distinct hemodynamic and wall mechanical profiles associated with favorable AVF remodeling. Enhancing NOS3 expression may be a potential therapeutic approach for promoting AVF maturation.
Highlights
Creation of a hemodialysis arteriovenous fistula (AVF) causes aberrant vascular mechanics at and near the AVF anastomosis
Because aggressive neointimal hyperplasia (NH) development often occurs at and near the anastomosis, we investigated the hemodynamic profile of this region (Figs 3 and 4) and compared it to the hemodynamics displayed by the proximal AVF vein (Fig. 5), which is less prone to NH
Our studies found that overexpression of NOS3 led to favorable AVF remodeling, smoother blood flow streamlines, as well as lower fluid shear stress at the wall, luminal fluid vorticity, circumferential inner wall stretch, and radial wall thinning
Summary
Creation of a hemodialysis arteriovenous fistula (AVF) causes aberrant vascular mechanics at and near the AVF anastomosis. Based on the wealth of literature regarding the effects of hemodynamics and wall mechanics on arterial wall function and remodeling, it has long been postulated that aberrant vascular mechanics may lead to NH formation and/or inadequate lumen dilation, and AVF maturation failure. Whether these relationships exist in the vein are not yet clear, as venous ECs and SMCs are known to have different phenotypes from their arterial counterparts[20,21,22]. We present the first MRI-based fluid-structure interaction (FSI) pipeline to characterize both hemodynamics and wall mechanics in murine AVFs with varying NOS3 expression levels in deformable blood vessel walls
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