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Dynamic and functional linkage between von Willebrand factor and ADAMTS-13 with aging: an Atherosclerosis Risk in Community study

血管性血友病因子 内科学 止血 瑞斯托西汀 抗原 ADAMTS13号 人口 纤维蛋白原 内分泌学 免疫学 化学 医学 血小板 环境卫生
作者
Wei Liu,Kavita Patel,Yi Wang,Michael Nodzenski,Ashley Nguyen,Gayle Teramura,Harrison A. Higgins,Ron C. Hoogeveen,David Couper,Xiaoyun Fu,Barbara A. Konkle,Matthew Shane Loop,Jing‐fei Dong
出处
期刊:Journal of Thrombosis and Haemostasis [Wiley]
卷期号:21 (12): 3371-3382 被引量:2
标识
DOI:10.1016/j.jtha.2023.07.023
摘要

Abstract

Background

von Willebrand factor (VWF) is a multimeric glycoprotein critically involved in hemostasis, thrombosis, and inflammation. VWF function is regulated by its antigen levels, multimeric structures, and the state of enzymatic cleavage. Population studies in the past have focused almost exclusively on VWF antigen levels in cross-sectional study designs.

Objective

To identify subjects in the Atherosclerosis Risk in Community study who had persistently low and high VWF antigen over 10 years and to quantify longitudinal changes in the biological activities and cleavage of VWF in these subjects.

Methods

We measured VWF antigen, propeptide, adhesive activities, and cleavage by ADAMTS-13 quantified using a mass spectrometry method that detected the cleaved VWF peptide EQAPNLVY, as well as coagulation factor VIII activity.

Results

We determined the mean subject-specific increase in VWF to be 22.0 International Units (IU)/dL over 10 years, with 95% between -0.3 and 59.7 IU/dL. This aging-related increase was also detected in VWF propeptide levels, ristocetin cofactor activity, and VWF binding to collagen. We identified 4.1% and 25.0% of subjects as having persistently low (<50 IU/dL) and high (>200 IU/dL) VWF antigen, respectively. Subjects with persistently low VWF had enhanced ristocetin cofactor activity, whereas those with persistently high VWF had elevated levels of ADAMTS-13, resulting in a comparable rate of VWF cleavage between the 2 groups.

Conclusions

These results provide new information about the effects of aging on VWF antigens and adhesive activity and identify a functional coordination between VWF and the rate of its cleavage by ADAMTS-13.

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