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Nrf2 in the Regulation of Endothelial Cell Homeostasis During Inflammation

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Nrf2 and its Modulation in Inflammation

Part of the book series: Progress in Inflammation Research ((PIR,volume 85))

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Abstract

Vascular endothelial cells line the inner surface of blood vessels, functioning as the selective barrier between the blood and internal organs. Inflammation in endothelial cells impairs vascular functions, such as barrier function and the control of blood pressure, and enhances the recruitment of leukocytes, resulting in cardiovascular disease or cerebrovascular disease. Vascular inflammation is often initiated by enhanced generation of reactive oxygen species (ROS) and provokes additional oxidative stress. The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) coordinately activates the expression of antioxidant and xenobiotic detoxifying genes, thereby protecting the vascular cells from oxidative stress. A number of studies have investigated the role of Nrf2 in endothelial cells and revealed that endothelial Nrf2 is activated not only by well-known electrophilic Nrf2 inducers such as sulforaphane in broccoli but also by mechanical shear stress and by circulating insulin-like growth factor (IGF)-1. Nrf2 is activated in the endothelial cells of straight segments of vessels that are exposed to unidirectional laminar flow (L-flow), thus contributing to the atheroprotective property of these areas. In contrast, Nrf2 activation is defective and unactivated in cells in branched segments that are exposed to disturbed flow; these areas are atheroprone. We review the mechanisms for endothelial Nrf2 activation via physiological stimuli and its effects on vascular biology, and we discuss the roles of Nrf2 target genes.

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  1. Department of Stress Response Science, Center for Advanced Medical Research, Hirosaki University Graduate School of Medicine, Hirosaki, Japan

    Hiromi Yamazaki & Ken Itoh

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    Huai Deng

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Yamazaki, H., Itoh, K. (2020). Nrf2 in the Regulation of Endothelial Cell Homeostasis During Inflammation. In: Deng, H. (eds) Nrf2 and its Modulation in Inflammation. Progress in Inflammation Research, vol 85. Springer, Cham. https://doi.org/10.1007/978-3-030-44599-7_4

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