Abstract 811: Eicosapentaenoic Acid Attenuates Aortic Medial Calcification in a Rat Model of Vascular Calcification
Background: Vascular calcification plays an important role in the development of cardiovascular disorders. Recent studies have revealed the many biological effects of eicosapentaenoic acid (EPA), a major n-3 polyunsaturated fatty acid, and its usefulness for treating atherosclerosis. Nevertheless, few studies have evaluated the effects of EPA on arterial medial calcification. This study was conducted to examine the effects of EPA on vascular calcification.
Methods and Results: As previously reported, arterial medial calcification was induced by treating 42-day-old Sprague-Dawley rats with warfarin and vitamin K1 for 2 weeks (WVK rats), to inhibit γ-carboxylation of matrix Gla protein. In addition, EPA rats were established by feeding EPA to WVK rats at the dose of 1 g/kg/day. Histological evaluation with von Kossa staining revealed that dramatic decrease of arterial medial calcification in EPA rats as compared with that in the WVK rats (histological calcification ratio: WVK vs. EPA=4.7±2.6 % vs. 1.8±1.4 %, p<0.05). Immunohistochemical and RT-PCR analyses revealed that the expressions of osteoblastic markers such as osteopontin, alkaline phosphatase, and cbfa1 were significantly increased in the WVK rats, while they were inhibited in the EPA rats. Immunohistochemistry for CD68 revealed significant migration of macrophages into the aortic adventitia around the calcified area, with a positive correlation noted between the cell number and the calcification ratio. Some of these macrophages showed positive immunohistochemical staining for matrix-metalloproteinase (MMP)-2 or MMP-9. EPA decreased this macrophage infiltration and also the mRNA expression of monocyte chemotactic protein (MCP)-1 in the aorta. Additionally, immunoblotting and gelatin zymography revealed decreased MMP-9 expression in the EPA rats as compared with that in the WVK rats.
Conclusion: These observations indicate that EPA attenuates arterial medial calcification not only by regulating the osteogenic process, but also by inhibiting MMP activity through suppression of macrophage infiltration in the rat model of vascular calcification.