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Transcription Factor NRF2 in Endothelial Functions

  • THE ROLE OF REDOX-DEPENDENT PROTEINS IN THE IMPLEMENTATION OF REDOX-REGULATION OF CELLS
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Abstract

The transcription factor NRF2 is a major regulator of cell antioxidant defense. NRF2 is activated by various stimuli, such as oxidants and electrophiles, to induce transcription of a number of genes whose products are involved in xenobiotic metabolism and contribute to the reduction of oxidative stress. NRF2 is one of the key transcription factors that ensure the endothelial cell function. The endothelium is a cell layer that lines the lumens of blood vessels and performs various homeostatic functions, controlling migration of leukocytes, regulating thrombosis and vascular tone, and playing a role in angiogenesis. Endothelial dysfunction is often accompanied by inflammation and oxidative stress, which may lead to cell aging and cell death by apoptosis, necrosis, or ferroptosis. Endothelial dysfunction contributes to the development of diabetes and common cardiovascular disorders, such as hypertension and atherosclerosis. Many pathophysiological processes in the endothelium, including senile changes, are associated with decreased NRF2 activity, leading to inflammatory activation and decreasing activity of the cell antioxidant defense systems. Activation of the NRF2 signaling pathway generally contributes to the resolution of inflammation and oxidative stress. The review focuses on the role that NRF2 plays in basic functions of the endothelium in normal and pathological conditions. Advantages and disadvantages of NRF2 activation as a way to prevent and treat cardiovascular diseases are discussed additionally.

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ACKNOWLEDGMENTS

We are grateful to A. Prikhod’ko for useful criticism and help in manuscript editing.

Funding

This work was supported by the Russian Science Foundation (project no. 23-14-00061).

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Authors and Affiliations

  1. Belozersky Institute of Physicochemical Biology, Moscow State University, 119991, Moscow, Russia

    N. D. Kondratenko & R. A. Zinovkin

  2. Pirogov Russian National Research Medical University, Russian Clinical Research Center for Gerontology, Ministry of Health of the Russian Federation, 129226, Moscow, Russia

    N. D. Kondratenko & R. A. Zinovkin

  3. Faculty of Bioengineering and Bioinformatics, Moscow State University, 119991, Moscow, Russia

    L. A. Zinovkina

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  1. N. D. Kondratenko
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Abbreviations: PKB (Akt), protein kinase B; ARE, antioxidant response element; BH4, tetrahydrobiopterin; PARK7 (DJ-1), Parkinson disease protein 7; eNOS, endothelial NO synthase; GCLC, glutamate-cysteine ligase catalytic subunit; GSH, glutathione; ICAM-1, intercellular adhesion molecule 1; KEAP1, Kelch-like ECH-associated protein 1; Maf , musculoaponeurotic fibrosarcoma transcription factor; Neh domain, NRF2-ECH homology domain; Nox4, NADPH oxidase 4; NRF2, nuclear factor erythroid-2-related factor 2; SQSTM1 (p62), sequestosome 1; PAPC, 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphocholine; VCAM-1, vascular cell adhesion molecule 1; β-TrCP, β-transducin repeat-containing protein; ROS, reactive oxygen species; CVD, cardiovascular disease; aa, amino acid residues (only with numbers).

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Kondratenko, N.D., Zinovkina, L.A. & Zinovkin, R.A. Transcription Factor NRF2 in Endothelial Functions. Mol Biol 57, 1052–1069 (2023). https://doi.org/10.1134/S0026893323060092

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