Study slices in tecplot 36011/13/2022 ![]() ![]() NO derived from endothelial nitric oxide synthase (eNOS, also known as NOS3) stimulates arterial 17 and venous 16, 17 vasorelaxation via increasing the generation of cyclic guanosine monophosphate (cGMP) to cause active smooth muscle relaxation, and inhibits arterial SMC migration and proliferation 25, 26, all of which could lead to favorable AVF development. Nitric oxide (NO) has been well-established as beneficial to vascular health and function 23, 24. Importantly, detailed hemodynamics and wall mechanics in the AVF are not yet fully available. However, 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. 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 ultimately AVF maturation failure. Such a drastic increase in volumetric blood flow, coupled with the acute change in blood flow direction at the anastomosis, causes drastically aberrant vascular mechanics (i.e., hemodynamics and wall mechanics) in the anastomotic region. The shunting of arterial flow into the vein decreases the resistance and thus causes the regional AVF flow to be 5- to 10-fold higher than normal arterial flow in patients 18, 19. Lumen expansion involves the relaxation of vascular SMCs upon stimulation by vasodilators released from endothelial cells (ECs) 14, 15, 16, 17. NH, which usually occurs at and near the AVF anastomosis, is primarily a result of vascular smooth muscle cells (SMCs) and fibroblasts migrating and proliferating from the vessel media into the intima 11, 13. ![]() The two main etiologies of AVF maturation failure are aggressive neointimal hyperplasia (NH) development and inadequate lumen expansion of the AVF vein 11, 12. Further, compared to patients dialyzing with a mature AVF, the relative mortality risk has been reported as 1.4 fold higher for patients using an AVG 6.Ĭurrently up to 60% of newly created AVFs do not successfully mature to become usable for hemodialysis 7, 8, 9, 10. If successfully matured for dialysis, an AVF is favored over an AVG due to its higher long-term patency and lower long-term intervention rates 5. Mortality rates in patients dialyzing with catheters have been reported to be 1.4 and 1.1 times greater than that in patients dialyzing with AVFs and AVGs, respectively 4. AVF maturation failure results in dialysis therapy with other types of vascular access including a tunneled dialysis catheter or a synthetic arteriovenous graft (AVG). However, AVF maturation failure remains a critically important clinical problem and currently there are no effective treatments to promote AVF maturation 1, 2, 3. The arteriovenous fistula (AVF), created by a direct anastomosis between a peripheral artery and vein, is the preferred choice of vascular access for hemodialysis patients. Enhancing NOS3 expression may be a potential therapeutic approach for promoting AVF maturation. ![]() Our results demonstrate that overexpression of NOS3 resulted in distinct hemodynamic and wall mechanical profiles associated with favorable AVF remodeling. 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. When compared to NOS3+/+ and NOS3−/−, AVFs in the OE mice had larger lumen area. 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+/+). We hypothesize that NOS3 promotes AVF maturation by regulating local vascular mechanics following AVF creation. 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. 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. Creation of a hemodialysis arteriovenous fistula (AVF) causes aberrant vascular mechanics at and near the AVF anastomosis. ![]()
0 Comments
Leave a Reply.AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |