Von Willebrand factor propeptide variants lead to impaired storage and ER retention in patient-derived endothelial colony-forming cells.

ABSTRACT:

Background

von Willebrand factor (VWF) is synthesized by vascular endothelial cells and megakaryocytes. The VWF propeptide is critical for multimerization and acts as an intra-molecular chaperone for mature VWF in sorting to its storage organelles, Weibel-Palade bodies (WPBs). In the Canadian Type 3 VWD study, almost half of the identified variants were in the VWF propeptide and these were associated with an increased bleeding phenotype.

Objective

To investigate VWF propeptide variants that cause quantitative von Willebrand disease (VWD) by utilizing patient-derived endothelial colony-forming cells (ECFCs).

Patients/methods

Endothelial colony-forming cells were isolated from five Type 3 VWD patients from four families with the following variants: (1) homozygous p.Asp7

SUBMITTER: Bowman M 

PROVIDER: S-EPMC9246936 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature