Coagulation cofactor von Willebrand factor promotes vascular calcification in patients with chronic renal failure and in a vascular calcification model

Vascular calcification and coagulation disorders are highly prevalent in patients with chronic renal failure (CRF); however, whether a causal relationship between these two exist is not clear. This study investigated the role of the coagulation factor von Willebrand factor (vWF) in the pathogenesis of vascular calcification in CRF. RNA sequencing was used to detect changes in gene expression involved in coagulation cascades in human umbilical vascular endothelial cells (HUVECs) treated with Na 2 HPO 4 and NaH 2 PO 4 , reaching a final total phosphate concentration of 3 mM. A rat model of vascular calcification was generated by feeding rats a diet containing 0.5% adenine and 1.2% phosphorus. vWF expression in HUVECs was determined using RT-qPCR and Western blot analyses. Gain- and loss- of function approaches were used to examine the effect of vWF on HUVEC calcification. A segment of radial artery and plasma of CRF patients were collected to analyze calcification and gene expression. The correlation between circulating levels of vWF and bone morphogenetic protein 2 (BMP2) was examined. vWF expression increased in Pi-treated HUVECs, which coincided with increased BMP2 expression. Circulating levels of vWF and BMP2 were significantly higher in CRF patients and in the vascular calcification rat compared to the respective controls. We found a positive correlation of vWF and BMP2. vWF promoted Pi-induced HUVEC calcification, which was attenuated by treatment with Noggin, an inhibitor of BMP signaling. These findings suggest that vWF promotes Pi-induced HUVEC calcification and vascular calcification in CRF, at least in part, through the involvement of BMP signaling.