title: Eicosapentaenoic acid reduces warfarin-induced arterial calcification in rats.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. saeko@research.twmu.ac.jp
authors.forename: Saeko
authors.initials: S
authors.lastname: Kanai
authors.forename: Kenta
authors.initials: K
authors.lastname: Uto
authors.forename: Kazuho
authors.initials: K
authors.lastname: Honda
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Hagiwara
authors.forename: Hideaki
authors.initials: H
authors.lastname: Oda
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D002114:Calcinosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D018932:Chemokine CCL2 / Q000096:biosynthesis; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D007083:Iliac Artery / Q000187:drug effects / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D010837:Vitamin K 1; D014859:Warfarin
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D014859:Warfarin; D010837:Vitamin K 1; D015118:Eicosapentaenoic Acid; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9