Transcription Factor NRF2 in Endothelial Functions

Abstract

The transcription factor NRF2 is the major regulator of cellular antioxidant defense. NRF2 is activated by various stimuli, such as oxidants and electrophiles, which induce the 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 for endothelial cell function. Endothelium is a cell layer lining the inner cavity of blood vessels, which performs various homeostatic functions: it controls migration of leukocytes, regulates thrombosis and vascular tone, and drives angiogenesis. Endothelial dysfunction is often accompanied by inflammation and oxidative stress, which may lead to cellular aging as well as cell death by apoptosis, necrosis, and ferroptosis. Endothelial dysfunction contributes to the development of such common cardiovascular diseases as hypertension, diabetes, and atherosclerosis. Many pathophysiological processes in the endothelium, including senile changes, are associated with decreased NRF2 activity, leading to inflammatory activation and decreased activity of cellular antioxidant defense systems. Activation of the NRF2 signaling pathway generally contributes to the resolution of inflammation and oxidative stress. This review focuses on the importance of NRF2 in the basic functions of endothelium in normal and pathological conditions. In addition, the advantages and disadvantages of NRF2 activation as a way to prevent and treat cardiovascular diseases are discussed.