von Willebrand Factor: A Central Regulator of Arteriovenous Fistula Maturation Through Smooth Muscle Cell Proliferation and Outward Remodeling

Author:

Laboyrie Suzanne L.1ORCID,de Vries Margreet R.2ORCID,de Jong Alwin2ORCID,de Boer Hetty C.1ORCID,Lalai Reshma A.1,Martinez Laisel3ORCID,Vazquez‐Padron Roberto I.3,Rotmans Joris I.1ORCID

Affiliation:

1. Internal Medicine Leiden University Medical Centre Leiden The Netherlands

2. Surgery Leiden University Medical Centre Leiden The Netherlands

3. Vascular Surgery University of Miami Miami FL

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 <0.0001). AVF flow in wild‐type mice was incremental over 2 weeks, whereas flow in vWF −/− mice did not increase, resulting in a two‐fold lower flow at 14 days compared with wild‐type mice ( P =0.016). Outward remodeling in matured patient AVFs coincided with increased local vWF expression in the media of the venous outflow tract. Absence of vWF in the intimal layer correlated with an increase in the intima‐media ratio. Conclusions vWF enhances AVF maturation because its positive effect on outward remodeling outweighs its stimulating effect on intimal hyperplasia.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3