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Nutrients 2015, 7(9), 8112-8126; doi:10.3390/nu7095381

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.
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)
View Full-Text   |   Download PDF [1206 KB, uploaded 21 September 2015]   |  

Abstract

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
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

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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