Eicosapentaenoic acid reduces warfarin-induced arterial calcification in rats

Atherosclerosis. 2011 Mar;215(1):43-51. doi: 10.1016/j.atherosclerosis.2010.12.001. Epub 2010 Dec 8.


Background: Eicosapentaenoic acid (EPA), a major n-3 polyunsaturated fatty acid, is reported to have various protective effects for cardiovascular disease. However, few studies have focused on the influence of EPA on vascular calcification.

Methods and results: Arterial medial calcification (AMC) was induced by administering warfarin (3 mg/g food) and vitamin K1 (1.5 mg/g food) for 2 weeks in Sprague-Dawley rats (control group), and EPA (1 g/kg/day) was administered for 2 weeks simultaneously with warfarin and vitamin K1 (EPA group) or after initiation of AMC (late EPA group). EPA showed a marked reduction of medial calcification in the EPA group, and showed a similar effect in the late EPA group. Immunohistochemical and RT-PCR analyses showed that EPA lowered the expression of osteogenetic markers, such as osteopontin, alkaline phosphatase and core binding factor-α1 in the aorta. Significant migration of macrophages with expression of matrix-metalloproteinase (MMP)-2 or MMP-9 was observed in the aortic adventitia around calcification. EPA also reduced macrophage infiltration, MMP-9 expression as well as gene expression of monocyte chemotactic protein (MCP)-1.

Conclusions: These observations indicate that EPA attenuates arterial medial calcification through an effect associated with the suppression of MMP-9 activity and inhibition of macrophage infiltration as well as osteogenic protein expression in warfarin-induced rat models.

MeSH terms

  • Animals
  • Aorta / drug effects
  • Aorta / pathology
  • Calcinosis / chemically induced
  • Calcinosis / pathology
  • Calcinosis / prevention & control*
  • Chemokine CCL2 / biosynthesis
  • Eicosapentaenoic Acid / pharmacology
  • Iliac Artery / drug effects
  • Iliac Artery / pathology
  • Male
  • Matrix Metalloproteinase 2 / biosynthesis
  • Matrix Metalloproteinase 9 / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Vitamin K 1
  • Warfarin


  • Ccl2 protein, rat
  • Chemokine CCL2
  • Warfarin
  • Vitamin K 1
  • Eicosapentaenoic Acid
  • Matrix Metalloproteinase 2
  • Mmp2 protein, rat
  • Matrix Metalloproteinase 9