Duality of n-3 Polyunsaturated Fatty Acids on Mcp-1 Expression in Vascular Smooth Muscle: A Potential Role of 4-Hydroxy Hexenal
Open/View files
Date
2015
Author(s)
Nagayama, Kohji
Morino, Katsutaro
Sekine, Osamu
Nakagawa, Fumiyuki
Iwasaki, Hirotaka
Okada, Takashi
Tawa, Masashi
Sato, Daisuke
Imamura, Takeshi
Nishio, Yoshihiko
Ugi, Satoshi
Kashiwagi, Atsunori
Okamura, Tomio
Maegawa, Hiroshi
Publisher
MDPI
The Harvard community has made this article openly available. Please share how this access benefits you.
Citation
Nagayama, 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.
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.
Other Available Sources
Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material (LAA), as set forth at Terms of Service
Collection