Abstract
Statins are competitive inhibitors of hydroxymethylglutaryl-CoA (HMG-CoA) reductase and have been used to treat elevated low-density lipoprotein cholesterol (LDL-C) for almost four decades. Antioxidant and anti-inflammatory properties which are independent of the lipid-lowering effects of statins, i.e., their pleiotropic effects, might be beneficial in the prevention or treatment of many diseases. This review discusses the antioxidant effects of statins achieved by modulating the nuclear factor erythroid 2 related factor 2/ heme oxygenase-1 (Nrf2/HO-1) pathway in different organs and diseases. Nrf2 and other proteins involved in the Nrf2/HO-1 signaling pathway have a crucial role in cellular responses to oxidative stress, which is a risk factor for ASCVD. Statins can significantly increase the DNA-binding activity of Nrf2 and induce the expression of its target genes, such as HO-1 and glutathione peroxidase) GPx, (thus protecting the cells against oxidative stress. Antioxidant and anti-inflammatory properties of statins, which are independent of their lipid-lowering effects, could be partly explained by the modulation of the Nrf2/HO-1 pathway.
Highlights
Statins are lipid-lowering drugs which inhibit the activity of the hydroxymethylglutarylCoA (HMG-CoA) reductase enzyme in the cholesterol synthesis pathway [1,2]
Statins are drugs with low-density lipoprotein cholesterol (LDL-C)-lowering effects and many pleiotropic effects [86]. They might be useful in the treatment of many diseases, cardiovascular disease (CVD) and cancer, kidney diseases, liver diseases, lung diseases, and neurodegenerative diseases
The nuclear factor erythroid 2-related factor 2 (Nrf2)/HO-1 signaling pathway is a protective antioxidative pathway that plays an important role in removing environmental and endogenous stressors; it is important in preventing the progression of different diseases
Summary
Statins are lipid-lowering drugs which inhibit the activity of the hydroxymethylglutarylCoA (HMG-CoA) reductase enzyme in the cholesterol synthesis pathway [1,2]. SIM can decrease both oxidized HDL and oxidized LDL particles in a concentration-dependent manner [21] Statins achieve their antioxidant activity by their effects on nuclear factor erythroid 2-related factor 2 (Nrf2), a protein consisting of 589 amino acids with 66.1 kDa molecular mass, which belongs to the group of redox-sensitive transcription factors. Studies have shown that statins can significantly increase the DNA-binding activity of Nrf and induce the expression of its target genes, such as HO-1 and GPX, protecting the cells against the detrimental effects of oxidative stress [38]. Mevastatin reduces TNF-α induced ICAM-1 expression via p47phox/Nox/ROS/c-Src/PDGFR_/PI3K/Akt/Nrf2/ARE/HO-1 - statins have anti-inflammatory effects in HPAEpiCs. Simultaneous use of atorvastatin and C3G could activate Nrf pathway and increase antioxidative effects including GCLC, NQO-1, and HO-1 and SOD activity removing superoxide radicals and improving atherosclerosis. It could be concluded that statins improve CVD by inducing an antioxidant HO-1 defense mechanism and remodeling of the myocardial structure [76], and have anti-atherosclerotic effects apart from lipid-lowering [77]
Sign-in/Register to view highlights & summary 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.
