Table 2.

Animal Studies (on Mice) on Association of Warfarin Use With Calcification

Study No.	Authors	Duration of Warfarin Therapy	Modality Used to Assess Calcification	Results
1	Howe AM, Webster WH6 (2000)	5–12 wk	Alizarin red technique	Extensive arterial calcification; cerebral arteries, veins, and capillaries not calcified.
2	Price et al7 (1998)	1–5 wk	Von Kossa staining, radiographs, visual inspection of the artery, northern blot analysis of MGP mRNA levels	Warfarin causes rapid calcification of the elastic lamellae in rat arteries and heart valves. Warfarin treatment markedly increased the levels of MGP mRNA and protein in calcifying arteries and decreased the level of MGP in serum.
3	Price et al8 (2000)	Group aged 20–42 d: 2 wk Group aged 10 mo: 4 wk	Von Kossa staining	Warfarin‐induced artery calcification is accelerated by growth and vitamin D.
4	Koos et al18 (2009)	4 wk	PCR analysis for MGP mRNA	Warfarin may decrease MGP serum levels and increased aortic valve calcifications.
5	Liu et al26 (2008)	4 wk	Von Kossa staining	Warfarin treatment led to elevation of SBP and aortic medial calcification. Chronic treatment also increased collagen, but decreased elastin, in the aorta.
6	Price et al9 (2006)	6 d	Staining of whole arteries with Alizarin red, Von Kossa staining of histological sections	Addition of warfarin to culture medium caused extensive Alizarin‐red staining for calcification in the living carotid artery segment, whereas no staining could be detected in living carotid arteries incubated in the same medium without warfarin.
7	Price et al33 (2001)	1 wk	Alizarin red staining	Doses of osteoprotegerin that inhibit bone resorption are able to potently inhibit the calcification of arteries that is induced by warfarin treatment.

Abbreviations: MGP, matrix γ‐carboxyglutamate protein; PCR, polymerase chain reaction; SBP, systolic blood pressure.