The Role of Macrophage Iron Overload and Ferroptosis in Atherosclerosis

Overview

Journal Biomolecules

Publisher MDPI

Specialties Biochemistry
Molecular Biology

Date 2022 Nov 24

PMID 36421722

Authors

Jiedong Ma

Hongqi Zhang

Yufei Chen

Xiaojin Liu

Jiamin Tian

Wei Shen

Affiliations

Soon will be listed here.

Abstract

Ferroptosis is a new type of cell death caused by iron-dependent lipid peroxidation. In recent years, it has been found that ferroptosis can promote the progression of atherosclerosis (AS). Macrophages have been proven to play multiple roles in the occurrence and development of AS. Iron is a necessary mineral that participates in different functions of macrophages under physiological conditions. But iron overload and ferroptosis in macrophages may promote the progression of AS. Herein, we summarize the role of iron overload and ferroptosis in macrophages in AS from the perspective of iron metabolism, and iron overload and ferroptosis are significant contributors to AS development.

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References

Chen Q, Lv J, Yang W, Xu B, Wang Z, Yu Z . Targeted inhibition of STAT3 as a potential treatment strategy for atherosclerosis. Theranostics. 2019; 9(22):6424-6442. PMC: 6771242. DOI: 10.7150/thno.35528. View

Haschka D, Hoffmann A, Weiss G . Iron in immune cell function and host defense. Semin Cell Dev Biol. 2021; 115:27-36. DOI: 10.1016/j.semcdb.2020.12.005. View

Bersuker K, Hendricks J, Li Z, Magtanong L, Ford B, Tang P . The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature. 2019; 575(7784):688-692. PMC: 6883167. DOI: 10.1038/s41586-019-1705-2. View

Chawla A, Boisvert W, Lee C, Laffitte B, Barak Y, Joseph S . A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. Mol Cell. 2001; 7(1):161-71. DOI: 10.1016/s1097-2765(01)00164-2. View

Ito F, Sono Y, Ito T . Measurement and Clinical Significance of Lipid Peroxidation as a Biomarker of Oxidative Stress: Oxidative Stress in Diabetes, Atherosclerosis, and Chronic Inflammation. Antioxidants (Basel). 2019; 8(3). PMC: 6466575. DOI: 10.3390/antiox8030072. View

Chang L, Chiang S, Chen S, Yu Y, Chou R, Chang W . Heme oxygenase-1 mediates BAY 11-7085 induced ferroptosis. Cancer Lett. 2017; 416:124-137. DOI: 10.1016/j.canlet.2017.12.025. View

Fuhrmann D, Mondorf A, Beifuss J, Jung M, Brune B . Hypoxia inhibits ferritinophagy, increases mitochondrial ferritin, and protects from ferroptosis. Redox Biol. 2020; 36:101670. PMC: 7452134. DOI: 10.1016/j.redox.2020.101670. View

Malhotra R, Wunderer F, Barnes H, Bagchi A, Buswell M, ORourke C . Hepcidin Deficiency Protects Against Atherosclerosis. Arterioscler Thromb Vasc Biol. 2018; 39(2):178-187. PMC: 6344241. DOI: 10.1161/ATVBAHA.118.312215. View

Sun X, Ou Z, Xie M, Kang R, Fan Y, Niu X . HSPB1 as a novel regulator of ferroptotic cancer cell death. Oncogene. 2015; 34(45):5617-25. PMC: 4640181. DOI: 10.1038/onc.2015.32. View

10.

Yang K, Song H, Yin D . PDSS2 Inhibits the Ferroptosis of Vascular Endothelial Cells in Atherosclerosis by Activating Nrf2. J Cardiovasc Pharmacol. 2021; 77(6):767-776. PMC: 8274586. DOI: 10.1097/FJC.0000000000001030. View

11.

Meng H, Wang Y, Ruan J, Chen Y, Wang X, Zhou F . Decreased Iron Ion Concentrations in the Peripheral Blood Correlate with Coronary Atherosclerosis. Nutrients. 2022; 14(2). PMC: 8781549. DOI: 10.3390/nu14020319. View

12.

Youssef L, Rebbaa A, Pampou S, Weisberg S, Stockwell B, Hod E . Increased erythrophagocytosis induces ferroptosis in red pulp macrophages in a mouse model of transfusion. Blood. 2018; 131(23):2581-2593. PMC: 5992863. DOI: 10.1182/blood-2017-12-822619. View

13.

Ma S, Henson E, Chen Y, Gibson S . Ferroptosis is induced following siramesine and lapatinib treatment of breast cancer cells. Cell Death Dis. 2016; 7:e2307. PMC: 4973350. DOI: 10.1038/cddis.2016.208. View

14.

Zou Y, Li H, Graham E, Deik A, Eaton J, Wang W . Cytochrome P450 oxidoreductase contributes to phospholipid peroxidation in ferroptosis. Nat Chem Biol. 2020; 16(3):302-309. PMC: 7353921. DOI: 10.1038/s41589-020-0472-6. View

15.

Recalcati S, Locati M, Gammella E, Invernizzi P, Cairo G . Iron levels in polarized macrophages: regulation of immunity and autoimmunity. Autoimmun Rev. 2012; 11(12):883-9. DOI: 10.1016/j.autrev.2012.03.003. View

16.

Guo L, Sakamoto A, Cornelissen A, Hong C, Finn A . Ironing-Out the Role of Hepcidin in Atherosclerosis. Arterioscler Thromb Vasc Biol. 2019; 39(3):303-305. PMC: 7001885. DOI: 10.1161/ATVBAHA.119.312369. View

17.

Shah R, Shchepinov M, Pratt D . Resolving the Role of Lipoxygenases in the Initiation and Execution of Ferroptosis. ACS Cent Sci. 2018; 4(3):387-396. PMC: 5879472. DOI: 10.1021/acscentsci.7b00589. View

18.

Bai T, Li M, Liu Y, Qiao Z, Wang Z . Inhibition of ferroptosis alleviates atherosclerosis through attenuating lipid peroxidation and endothelial dysfunction in mouse aortic endothelial cell. Free Radic Biol Med. 2020; 160:92-102. DOI: 10.1016/j.freeradbiomed.2020.07.026. View

19.

Marcil V, Lavoie J, Emonnot L, Seidman E, Levy E . Analysis of the effects of iron and vitamin C co-supplementation on oxidative damage, antioxidant response and inflammation in THP-1 macrophages. Clin Biochem. 2011; 44(10-11):873-83. DOI: 10.1016/j.clinbiochem.2011.04.012. View

20.

Yu W, Liu W, Xie D, Wang Q, Xu C, Zhao H . High Level of Uric Acid Promotes Atherosclerosis by Targeting NRF2-Mediated Autophagy Dysfunction and Ferroptosis. Oxid Med Cell Longev. 2022; 2022:9304383. PMC: 9038411. DOI: 10.1155/2022/9304383. View