ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on Twitter

Kidney Week

Abstract: PO0528

The Effect of the Warfarin-TG2-MVs Axis in Vascular Calcification

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic


  • Liu, Yuqiu, Institute of Nephrology, Zhong Da Hospital, Southeast University, School of Medicine, Nanjing, China
  • Zhang, Xiaoliang, Institute of Nephrology, Zhong Da Hospital, Southeast University, School of Medicine, Nanjing, China

Warfarin is a common anticoagulant drug. How to effectively reduce vascular calcification induced by warfarin while ensuring its anticoagulant effect is an urgent problem to be solved. Previous studies have found that warfarin enhances the expression and activity of transglutaminase 2 (TG2) in vascular smooth muscle cells (VSMCs), which mediates communication between cells and extracellular matrix (ECM). Matrix vesicles (MVs) are the center of hydroxyapatite crystal precipitation, which is released to ECM and interacts with ECM protein to initiate mineralization and form calcification core. This study observed the role of warfarin-TG2-MVs axis in vascular calcification by culturing VSMCs in vitro.


VSMCs were cultured in normal or osteogenic medium (OM) and stimulated with 10 μm warfarin for 3-14 days. The expressions of SM22α, Runx2, ALP, OPN and OPG were detected by RT-PCR, Western blot. Alizarin red and von Kossa staining were performed to evaluate calcification, and calcium content was determined. Meanwhile, the expression and activity of TG2 were detected. Differential centrifugation was used to extract MVs and evaluate their release. Type I collagen was coated in the culture dish to determine the calcification of MV-collagen.


Warfarin stimulation promoted transdifferentiation of VSMCs, that the expression of osteogenic factors Runx2, ALPL and OPN were increased, while the expression of SM22α and calcification inhibitor OPG were decreased. When using OM, the above trend was more obvious. Alizarin red and von Kossa staining were performed when the cells were cultured for 14 days. The results of calcium staining in the warfarin intervention group were all positive. Warfarin promoted the expression and activity of TG2, and it gradually increased with the extension of the intervention time. The same amount of cells were cultured for 7 days under different stimuli, and the medium was changed every other day. Then, the supernatant was collected for differential centrifugation. The amount of MVs produced by the warfarin and OM group was significantly higher than that of other groups, and the ability to mineralize of MVs in type I collagen was increased.


Warfarin increased the expression and activity of TG2, promoted the release of MVs from VSMCs, and further cross-linked ECM to aggravate vascular calcification.