Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 May 27;25(11):5831.
doi: 10.3390/ijms25115831.

Nrf2 Signaling Pathway as a Key to Treatment for Diabetic Dyslipidemia and Atherosclerosis

Michelle Yi  1 , Arvin John Toribio  1 , Yusuf Muhammad Salem  1 , Michael Alexander  1 , Antoney Ferrey  2 , Lourdes Swentek  1 , Ekamol Tantisattamo  2 , Hirohito Ichii  1
Affiliations
Review

Nrf2 Signaling Pathway as a Key to Treatment for Diabetic Dyslipidemia and Atherosclerosis

Michelle Yi et al. Int J Mol Sci. .

Abstract

Diabetes mellitus (DM) is a chronic endocrine disorder that affects more than 20 million people in the United States. DM-related complications affect multiple organ systems and are a significant cause of morbidity and mortality among people with DM. Of the numerous acute and chronic complications, atherosclerosis due to diabetic dyslipidemia is a condition that can lead to many life-threatening diseases, such as stroke, coronary artery disease, and myocardial infarction. The nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway is an emerging antioxidative pathway and a promising target for the treatment of DM and its complications. This review aims to explore the Nrf2 pathway's role in combating diabetic dyslipidemia. We will explore risk factors for diabetic dyslipidemia at a cellular level and aim to elucidate how the Nrf2 pathway becomes a potential therapeutic target for DM-related atherosclerosis.

Keywords: Nrf2 pathway; antioxidant; atherosclerosis; diabetes mellitus; dyslipidemia; oxidative stress.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Graphical abstract summarizing the general flow of the development of DM-induced atherosclerotic cardiovascular diseases, with and without the Nrf2 pathway activation: Nrf2, nuclear erythroid 2-related factor 2.
Figure 2
Figure 2
Antioxidative roles of Nrf2 in DM-induced oxidative stress and atherosclerotic progression viewed at the molecular level: Keap1, Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1; Nrf2, nuclear erythroid 2-related factor 2; ARE, antioxidant response element; NQO1, NAD(P)H:quinone oxidoreductase 1; Trx, thioredoxin; HO-1, heme oxygenase 1; DM, diabetes mellitus.
Figure 3
Figure 3
Overall mechanisms of the development of the highlighted risk factors and atherosclerosis in DM environment: HL, hepatic lipase; HSL, hormone-sensitive lipase; LPL, lipoprotein lipase; sdLDL, small dense low-density lipoprotein; VLDL, very-low-density lipoprotein; LSR, lipolysis-stimulated lipoprotein receptor; oxLDL, oxidized low-density lipoprotein; ox-sdLDL, oxidized small dense low-density lipoprotein; LOX-1, lectin-like oxidized LDL receptor-1.
Figure 4
Figure 4
Overall mechanisms of plaque accumulation and inflammation of arterial walls caused by increased atherosclerotic lipoproteins: sdLDL, small dense low-density lipoprotein; ox-sdLDL, oxidized small dense low-density lipoprotein; oxLDL, oxidized low-density lipoprotein; VLDL, very-low-density lipoprotein; LOX-1, lectin-like oxidized LDL receptor-1; VLDLR, very-low-density lipoprotein.
See this image and copyright information in PMC

References

    1. Hoogeveen R.C., Gaubatz J.W., Sun W., Dodge R.C., Crosby J.R., Jiang J., Couper D., Virani S.S., Kathiresan S., Boerwinkle E., et al. Small dense low-density lipoprotein-cholesterol concentrations predict risk for coronary heart disease: The atherosclerosis risk in communities (aric) study. Arterioscler. Thromb. Vasc. Biol. 2014;34:1069–1077. doi: 10.1161/ATVBAHA.114.303284. - DOI - PMC - PubMed
    1. Qi Y., Liu J., Wang W., Wang M., Zhao F., Sun J., Liu J., Deng Q., Zhao D. High sdldl cholesterol can be used to reclassify individuals with low cardiovascular risk for early intervention: Findings from the chinese multi-provincial cohort study. J. Atheroscler. Thromb. 2020;27:695–710. doi: 10.5551/jat.49841. - DOI - PMC - PubMed
    1. Ference B.A., Kastelein J.J.P., Ray K.K., Ginsberg H.N., Chapman M.J., Packard C.J., Laufs U., Oliver-Williams C., Wood A.M., Butterworth A.S., et al. Association of triglyceride-lowering lpl variants and ldl-c-lowering ldlr variants with risk of coronary heart disease. JAMA. 2019;321:364–373. doi: 10.1001/jama.2018.20045. - DOI - PMC - PubMed
    1. Orchard T.J., Costacou T., Kretowski A., Nesto R.W. Type 1 diabetes and coronary artery disease. Diabetes Care. 2006;29:2528–2538. doi: 10.2337/dc06-1161. - DOI - PubMed
    1. Yang H., Jin X., Kei Lam C.W., Yan S.K. Oxidative stress and diabetes mellitus. Clin. Chem. Lab. Med. 2011;49:1773–1782. doi: 10.1515/cclm.2011.250. - DOI - PubMed

Substances