Role of NFAT in the Progression of Diabetic Atherosclerosis

Abstract

Nuclear factor of activated T cells (NFAT) is a transcription factor with a multidirectional regulatory function, that is widely expressed in immune cells, including cells in the cardiovascular system, and non-immune cells. A large number of studies have confirmed that calcineurin/NFAT signal transduction is very important in the development of vascular system and cardiovascular system during embryonic development, and plays some role in the occurrence of vascular diseases such as atherosclerosis, vascular calcification, and hypertension. Recent in vitro and in vivo studies have shown that NFAT proteins and their activation in the nucleus and binding to DNA-related sites can easily ɨnduce the expression of downstream target genes that participate in the proliferation, migration, angiogenesis, and vascular inflammation of vascular wall related cells in various pathophysiological states. NFAT expression is regulated by various signaling pathways, including CD137-CD137L, and OX40-OX40L pathways. As a functionally diverse transcription factor, NFAT interacts with a large number of signaling molecules to modulate intracellular and extracellular signaling pathways. These NFAT-centered signaling pathways play important regulatory roles in the progression of atherosclerosis, such as in vascular smooth muscle cell phenotypic transition and migration, endothelial cell injury, macrophage-derived foam cell formation, and plaque calcification. NFAT and related signaling pathways provide new therapeutic targets for vascular diseases such as atherosclerosis. Hence, further studies of the mechanism of NFAT in the occurrence and evolution of atherosclerosis remain crucial.

A review: Pharmacology and pharmacokinetics of Schisandrin A

“…Nuclear factor of activated T cells (NFAT) is a family of transcription factors that play a critical role in the development and function of the immune system (Macian, 2005). Several studies have shown that the development of various diseases such as autoimmune diseases, cholestatic liver injury, diabetes mellitus, and rectal cancer are associated with NFAT activation (Cai et al, 2021; Cai, Yu, Soroka, Wang, & Boyer, 2021; Gang et al, 2019; Lee, Kim, & Choi, 2018). Lee et al found that SA isolated from the Chinese herb Schisandra chinensis inhibited NFAT with a half maximal inhibitory concentration (IC50) of 7.23 ± 0.21 μM (Lee et al, 2003).…”

Nutrigenomic Effect of Hydroxytyrosol in Vascular Endothelial Cells: A Transcriptomic Profile Analysis

“…Upon challenge with an inflammatory stimulus, calcineurin dephosphorylates NFAT, causing it to shuttle to the nucleus, where it increases the transcription of inflammatory genes [56]. NFAT signaling pathways play an essential role in regulating inflammatory mediators, extracellular matrix proteins, vascular permeability, and adhesion molecules involved in the progression of atherosclerosis [57]. Based on our microarray results, the expression of NFATC1 member was decreased by HT treatment in inflamed endothelial cells.…”

Sex differences in coronary artery disease and diabetes revealed by scRNA-Seq and CITE-Seq of human CD4+ T cells

“…NFAT is involved in vascular smooth muscle cell phenotypic transition and migration, endothelial cell injury, macrophage-derived foam cell formation, and plaque calcification. 34 Only in CAD, but not in DM, the “Cytotoxic T Lymphocyte-mediated Apoptosis of Target cells” pathway was highly upregulated, and “T cell exhaustion signaling” pathway was downregulated. In DM, “IL-8 signaling”, “Integrin signaling” and “Ephrin receptor signaling” pathways were highly and uniquely upregulated.…”