1. von Willebrand Factor: A Central Regulator of Arteriovenous Fistula Maturation Through Smooth Muscle Cell Proliferation and Outward Remodeling
- Author
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Suzanne L. Laboyrie, Margreet R. de Vries, Alwin de Jong, Hetty C. de Boer, Reshma A. Lalai, Laisel Martinez, Roberto I. Vazquez‐Padron, and Joris I. Rotmans
- Subjects
AVF maturation ,intimal hyperplasia ,outward remodeling ,von Willebrand Factor ,VSMC ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Arteriovenous fistula (AVF) maturation failure is a main limitation of vascular access. Maturation is determined by the intricate balance between outward remodeling and intimal hyperplasia, whereby endothelial cell dysfunction, platelet aggregation, and vascular smooth muscle cell (VSMC) proliferation play a crucial role. von Willebrand Factor (vWF) is an endothelial cell–derived protein involved in platelet aggregation and VSMC proliferation. We investigated AVF vascular remodeling in vWF‐deficient mice and vWF expression in failed and matured human AVFs. Methods and Results Jugular‐carotid AVFs were created in wild‐type and vWF−/− mice. AVF flow was determined longitudinally using ultrasonography, whereupon AVFs were harvested 14 days after surgery. VSMCs were isolated from vena cavae to study the effect of vWF on VSMC proliferation. Patient‐matched samples of the basilic vein were obtained before brachio‐basilic AVF construction and during superficialization or salvage procedure 6 weeks after AVF creation. vWF deficiency reduced VSMC proliferation and macrophage infiltration in the intimal hyperplasia. vWF−/− mice showed reduced outward remodeling (1.5‐fold, P=0.002) and intimal hyperplasia (10.2‐fold, P
- Published
- 2022
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