Abstract
The transcription factor Nrf2 is a master regulator of multiple cytoprotective genes that maintain redox homeostasis and exert anti-inflammatory functions. The Nrf2-Keap1 signaling pathway is a paramount target of many cardioprotective strategies, because redox homeostasis is essential in cardiovascular health. Nrf2 gene variations, including single nucleotide polymorphisms (SNPs), are correlated with cardiometabolic diseases and drug responses. SNPs of Nrf2, KEAP1, and other related genes can impair the transcriptional activation or the activity of the resulting protein, exerting differential susceptibility to cardiometabolic disease progression and prevalence. Further understanding of the implications of Nrf2 polymorphisms on basic cellular processes involved in cardiometabolic diseases progression and prevalence will be helpful to establish more accurate protective strategies. This review provides insight into the association between the polymorphisms of Nrf2-related genes with cardiometabolic diseases. We also briefly describe that SNPs of Nrf2-related genes are potential modifiers of the pharmacokinetics that contribute to the inter-individual variability.
Highlights
On the other hand, attenuated SOD2 activity in those patients carrying the rs4880 polymorphism affects redox homeostasis and increases the cardiovascular risk associated with type 2 diabetes mellitus (T2DM) and inflammatory response related to the ox-LDL, which contributes to the onset and progression of atherosclerosis [84]
single nucleotide polymorphisms (SNPs) of nuclear factor erythroid2-related factor 2 (Nrf2) and related genes contribute to susceptibility for obesity, inflammation, and diabetes progression, as well as coronary artery disease, hypertension, and cardiovascular mortality
The endogenous antioxidant system deficiency is associated with several diseases; the influence of the genetic variation in Nrf2 and antioxidant eledant response elements (ARE)-containing genes that can impair the induction of the Nrf2-driven pathway accounts for susceptibility to suffer cardiometabolic diseases
Summary
A common feature of cardiometabolic diseases is the imbalance between pro- and anti-oxidative factors in the cell Such condition is associated with high levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that react with lipids, proteins, DNA, or activate redox signaling pathways, leading to cellular injury and death. Neh domain is located at the aminoterminal and has ETGE and DLG motifs that interact with Kelch-like ECH-associated protein 1 (Keap1), the well-known negative regulator of Nrf2 [20]. Neh and Neh domains act as negative regulators, and Neh interacts with the retinoic X receptor alpha (RXRα) to repress Nrf transcriptional activity. After heterodimerization with sMAF, Nrf induces the expression of antioxidant response-related genes [45] Another potential mechanism for Nrf activation involves its phosphorylation by several kinases.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
