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Open AccessArticle

Duality of n-3 Polyunsaturated Fatty Acids on Mcp-1 Expression in Vascular Smooth Muscle: A Potential Role of 4-Hydroxy Hexenal

1
Department of Medicine, Shiga University of Medical Science, Shiga 520-2192, Japan
2
Osaka Laboratory, JCL Bioassay Corporation, 5-16-26, Minamisuita, Suita-shi, Osaka 564-0043, Japan
3
Sunstar Inc., 3-1 Asahi-machi, Takatsuki, Osaka 569-1195, Japan
4
Joslin Diabetes Centre, Harvard Medical School, MA 02115, USA
5
Department of Pharmacology, Shiga University of Medical Science, Shiga 520-2192, Japan
6
Department of Diabetes and Endocrine Medicine, Kagoshima University, Kagoshima 890-8580, Japan
7
Kusatsu General Hospital, 1660, Yabase-cho, Kusatsu, Shiga 525-8585, Japan
*
Author to whom correspondence should be addressed.
Nutrients 2015, 7(9), 8112-8126; https://doi.org/10.3390/nu7095381
Received: 22 May 2015 / Revised: 24 August 2015 / Accepted: 31 August 2015 / Published: 21 September 2015
(This article belongs to the Special Issue DHA for Optimal Health)
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. View Full-Text
Keywords: monocyte chemotactic protein 1; 4-hydroxy hexenal; docosahexaenoic acid; eicosapentaenoic acid monocyte chemotactic protein 1; 4-hydroxy hexenal; docosahexaenoic acid; eicosapentaenoic acid
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Nagayama, K.; Morino, K.; Sekine, O.; Nakagawa, F.; Ishikado, A.; Iwasaki, H.; Okada, T.; Tawa, M.; Sato, D.; Imamura, T.; Nishio, Y.; Ugi, S.; Kashiwagi, A.; Okamura, T.; Maegawa, H. Duality of n-3 Polyunsaturated Fatty Acids on Mcp-1 Expression in Vascular Smooth Muscle: A Potential Role of 4-Hydroxy Hexenal. Nutrients 2015, 7, 8112-8126.

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