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Ishikado, Atsushi

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Ishikado

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Atsushi

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Ishikado, Atsushi
Author's Publications: search.filters.isAuthorOfPublication.6573f272-f9e8-4974-bf07-49100771ba0c

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    Duality of n-3 Polyunsaturated Fatty Acids on Mcp-1 Expression in Vascular Smooth Muscle: A Potential Role of 4-Hydroxy Hexenal
    (MDPI, 2015) Nagayama, Kohji; Morino, Katsutaro; Sekine, Osamu; Nakagawa, Fumiyuki; Ishikado, Atsushi; Iwasaki, Hirotaka; Okada, Takashi; Tawa, Masashi; Sato, Daisuke; Imamura, Takeshi; Nishio, Yoshihiko; Ugi, Satoshi; Kashiwagi, Atsunori; Okamura, Tomio; Maegawa, Hiroshi
    N-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have protective effects against atherosclerosis. Monocyte chemotactic protein (MCP)-1 is a major inflammatory mediator in the progression of atherosclerosis. However, little is known about the regulation of Mcp-1 by DHA and EPA in vessels and vascular smooth muscle cells (VSMCs). In this study, we compared the effect of DHA and EPA on the expression of Mcp-1 in rat arterial strips and rat VSMCs. DHA, but not EPA, suppressed Mcp-1 expression in arterial strips. Furthermore, DHA generated 4-hydroxy hexenal (4-HHE), an end product of n-3 polyunsaturated fatty acids (PUFAs), in arterial strips as measured by liquid chromatography-tandem mass spectrometry. In addition, 4-HHE treatment suppressed Mcp-1 expression in arterial strips, suggesting 4-HHE derived from DHA may be involved in the mechanism of this phenomenon. In contrast, Mcp-1 expression was stimulated by DHA, EPA and 4-HHE through p38 kinase and the Keap1-Nuclear factor erythroid-derived 2-like 2 (Nrf2) pathway in VSMCs. In conclusion, there is a dual effect of n-3 PUFAs on the regulation of Mcp-1 expression. Further study is necessary to elucidate the pathological role of this phenomenon.