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. 2016 Sep 5:786:10-18.
doi: 10.1016/j.ejphar.2016.05.022. Epub 2016 May 19.

Vitamin K2 regression aortic calcification induced by warfarin via Gas6/Axl survival pathway in rats

Xiaoyu Jiang  1 , Huiren Tao  2 , Cuiting Qiu  1 , Xiaolei Ma  1 , Shan Li  1 , Xian Guo  1 , Anlin Lv  3 , Huan Li  4
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Vitamin K2 regression aortic calcification induced by warfarin via Gas6/Axl survival pathway in rats

Xiaoyu Jiang et al. Eur J Pharmacol. .

Abstract

The aim of this study was to investigate the effect of vitamin K2 on aortic calcification induced by warfarin via Gas6/Axl survival pathway in rats. A calcification model was established by administering 3mg/g warfarin to rats. Rats were divided into 9 groups: control group (0W, 4W, 6W and 12W groups), 4W calcification group, 6W calcification group, 12W calcification group, 6W calcification+6W normal group and 6W calcification+6W vitamin K2 group. Alizarin red S staining measured aortic calcium depositions; alkaline phosphatase activity in serum was measured by a kit; apoptosis was evaluated by TUNEL assay; protein expression levels of Gas6, Axl, phosphorylated Akt (p-Akt), and Bcl-2 were determined by western blotting. The calcium content, calcium depositions, ALP activity and apoptosis were significantly higher in the calcification groups than control group. Gas6, Axl, p-Akt and Bcl-2 expression was lower in the calcification group than control group. 100μg/g vitamin K2 treatment decreased calcium depositions, ALP activity and apoptosis significantly, but increased Gas6, Axl, p-Akt and Bcl-2 expression. 100μg/g vitamin K2 reversed 44% calcification. Pearson correlation analysis showed a positive correlation between formation calcification and apoptosis (R(2)=0.8853, P<0.0001). In conclusion, we established a warfarin-induced calcification model and showed vitamin K2 can inhibit warfarin-induced aortic calcification and apoptosis. The regression of aortic calcification by vitamin K2 involved the Gas6/Axl axis. This data may provide a theoretical basis for future clinical treatments for aortic calcification.

Keywords: Arterial calcification mechanism; Cell apoptosis; Growth arrest specific gene 6 protein (Gas6); Vitamin K2.

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