NRF2-Related Epigenetic Modifications in Cardiac and Vascular Complications of Diabetes Mellitus

Abstract

Diabetes mellitus (DM) is a highly prevalent chronic disease that is accompanied with serious complications, especially cardiac and vascular complications. Thus, there is an urgent need to identify new strategies to treat diabetic cardiac and vascular complications. Nuclear factor erythroid 2-related factor 2 (NRF2) has been verified as a crucial target for the prevention and treatment of diabetic complications. The function of NRF2 in the treatment of diabetic complications has been widely reported, but the role of NRF2-related epigenetic modifications remains unclear. The purpose of this review is to summarize the recent advances in targeting NRF2-related epigenetic modifications in the treatment of cardiac and vascular complications associated with DM. We also discuss agonists that could potentially regulate NRF2-associated epigenetic mechanisms. This review provides a better understanding of strategies to target NRF2 to protect against DM-related cardiac and vascular complications.

Hypoglycemia, Vascular Disease and Cognitive Dysfunction in Diabetes: Insights from Text Mining-Based Reconstruction and Bioinformatics Analysis of the Gene Networks

“…The products of these genes encode insulin (INS) and insulin receptor (INSR), endothelin-1 (EDN1), erythropoietin (EPO), adiponectin (ADIPOQ), interleukin-1β (IL1B), interleukin-6 (IL6), tumor necrosis factor α (TNF), glucagon-like peptide-1 receptor (GLP1R), insulin-like growth factor-1 (IGF1), vascular endothelial growth factor A (VEGFA), C-reactive protein (CRP), nuclear factor, erythroid 2 like 2 (NFE2L2) and neuropeptide Y (NPY). A wide range of biological activities of these molecules is consistent with the concept of their key role in the pathophysiology of diabetic vascular complications [44][45][46][47][48][49][50][51][52][53][54][55][56].…”

Beneficial Health Effects of Glucosinolates-Derived Isothiocyanates on Cardiovascular and Neurodegenerative Diseases

“…PEITC caused reverse cholesterol transport via upregulating the peroxisome proliferator-activated receptor gamma (PPARγ)-LXR-α-ABCA1 pathway and inhibited ensuing atherosclerotic plaque inflammation through epigenetic modification of HDAC3 and NF-κB genes [ 80 ]. Again, PEITC enhanced epigenetic regulation of Nrf2 expression through H3K4me1 enrichment of the promoter region of Nrf2 gene (NFE2L2) and because of this, it was proposed that PEITC may relieve cardiovascular complication in DM [ 81 ]. Some authors recommended that PEITC should be investigated as a HDAC inhibitor for possible use in heart failure [ 156 ].…”

“…Key pathways in CVDs are modulated by PEITC as shown, with epigenetic modulation of some genes that in turn caused suppression of atherosclerotic plaque formation. In addition, PEITC reduced weight gain and alleviated features of DM [ 81 ]. Here, we urge more researches in its cardiovascular role.…”

LncRNAs regulate ferroptosis to affect diabetes and its complications

“…Immunofluorescence analysis showed that the fluorescence intensity of renal tubules in diabetic mice was significantly weaker than that in normal mice, indicating that the protein expression of Nrf2 in diabetic patients was reduced. Li et al found that the protein and mRNA expression levels of Nrf2 in the renal tubules of diabetic mice in the DM group were significantly lower than those in the NC group, as determined by immunofluorescence analysis, western blotting and qRT–PCR analysis ( Dodson et al, 2019 ; Wang et al, 2021 ; Zhao et al, 2021 ). When Nrf2 was knocked down in cells, the protein expression levels of GPX4, SLC7A11 and FTH-1 were significantly reduced and TFR-1 was increased.…”