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Effects of Eicosapentaenoic Acid on the Cytoprotection Through Nrf2-Mediated Heme Oxygenase-1 in Human Endothelial Cells

Lee, Seung Eun PhD; Kim, Gun-Dong PhD; Yang, Hana PhD; Son, Gun Woo MS; Park, Hye Rim MS; Cho, Jeong-Je MD, PhD; Ahn, Hyun-Jong PhD; Park, Cheung-Seog PhD; Park, Yong Seek PhD

Journal of Cardiovascular Pharmacology: July 2015 - Volume 66 - Issue 1 - p 108–117
doi: 10.1097/FJC.0000000000000251
Original Article

Abstract: Consumption of omega-3 polyunsaturated fatty acid, particularly eicosapentaenoic acid (EPA), is associated with a significant reduction in the risk of developing cardiovascular disease. The aim of this study was to investigate whether heme oxygenase-1 (HO-1) induction contributes to the cytoprotective effects of EPA in endothelial cells threatened with oxidative damage. In this study, we investigated the effect of EPA on the induction of HO-1 by NF-E2-related factor 2 (Nrf2) in human umbilical vein endothelial cells. In cells treated with low concentrations of EPA (10–25 μM), HO-1 expression increased in a time- and concentration-dependent manner. Additionally, EPA treatment increased Nrf2 nuclear translocation and antioxidant response element activity, leading to the upregulation of HO-1 expression. Furthermore, treatment with EPA reduced hydrogen peroxide (H2O2)-induced cell death. The reduction in cell death was reversed by treatment with zinc protoporphyrin, an inhibitor of HO-1, indicating that HO-1 contributed to the protective effect of EPA. These data suggest that EPA protects against H2O2-induced oxidative stress in endothelial cells by activating Nrf2 and inducting HO-1 expression.

Department of Microbiology, School of Medicine, Kyung Hee University, Seoul, Korea.

Reprints: Yong Seek Park, PhD, Department of Microbiology, School of Medicine, Kyung Hee University, No. 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Korea (e-mail:

Supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2011-0030072).

The authors report no conflicts of interest.

Received October 27, 2014

Accepted March 05, 2015

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