Health & Environmental Research Online (HERO)


Print Feedback Export to File
7317261 
Journal Article 
Eicosapentaenoic acid reduces warfarin-induced arterial calcification in rats 
Kanai, S; Uto, K; Honda, K; Hagiwara, N; Oda, H 
2011 
Yes 
Atherosclerosis
ISSN: 0021-9150
EISSN: 1879-1484 
215 
1 
43-51 
English 
21193197 
WOS:000288008700007 
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. 
Arterial medial calcification; Eicosapentaenoic acid; Macrophage; MCP-1; MMP-9; alkaline phosphatase; gelatinase A; gelatinase B; icosapentaenoic acid; monocyte chemotactic protein 1; osteopontin; phytomenadione; transcription factor RUNX2; warfarin; adventitia; animal cell; animal experiment; animal model; animal tissue; aorta; artery calcification; article; blood sampling; cell infiltration; controlled study; drug effect; drug induced disease; enzyme activity; gene expression; histopathology; immunohistochemistry; macrophage migration; male; nonhuman; priority journal; protein expression; rat; reverse transcription polymerase chain reaction; Animals; Aorta; Calcinosis; Chemokine CCL2; Eicosapentaenoic Acid; Iliac Artery; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Rats; Rats, Sprague-Dawley; Vitamin K 1; Warfarin