Nagayama, KohjiMorino, KatsutaroSekine, OsamuNakagawa, FumiyukiIshikado, AtsushiIwasaki, HirotakaOkada, TakashiTawa, MasashiSato, DaisukeImamura, TakeshiNishio, YoshihikoUgi, SatoshiKashiwagi, AtsunoriOkamura, TomioMaegawa, Hiroshi2015-11-032015Nagayama, K., K. Morino, O. Sekine, F. Nakagawa, A. Ishikado, H. Iwasaki, T. Okada, et al. 2015. “Duality of n-3 Polyunsaturated Fatty Acids on Mcp-1 Expression in Vascular Smooth Muscle: A Potential Role of 4-Hydroxy Hexenal.” Nutrients 7 (9): 8112-8126. doi:10.3390/nu7095381. http://dx.doi.org/10.3390/nu7095381.2072-6643http://nrs.harvard.edu/urn-3:HUL.InstRepos:23474051N-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.en-USmonocyte chemotactic protein 14-hydroxy hexenaldocosahexaenoic acideicosapentaenoic acidJournal Article2015-11-0310.3390/nu7095381