HMOX1 upregulation promotes ferroptosis in diabetic atherosclerosis

Meng, Zhijun; Liang, Hongping; Zhao, Jianli; Gao, Jiajia; Liu, Caihong; Ma, Xin‐Liang; Liu, Jing; Liang, Bin; Jiao, Xiangying; Cao, Ji-Min

doi:10.1016/j.lfs.2021.119935

Cited by 95 publications

(74 citation statements)

References 65 publications

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“…A recent study treated primary mouse aortic endothelial cells (MAECs) and human umbilical vein endothelial cells (HUVECs) with high glucose/high lipids (HGHL). It unveiled that HMOX1 plays a pivotal role in regulating diabetes-induced ferroptosis in endothelial injury ( 50 ). Consistently, our study confirmed that HMOX1 also displays a pro-ferroptotic effect on VSMCs.…”

Section: Discussionmentioning

confidence: 99%

Identification of HMOX1 as a Critical Ferroptosis-Related Gene in Atherosclerosis

Wang

et al. 2022

Front. Cardiovasc. Med.

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Ferroptosis is a novel form of programmed iron-dependent cell death. The ferroptosis-related genes (FRGs) have been recognized as biomarkers for cancers. Increasing evidence has indicated that ferroptosis is involved in the process of atherosclerosis. However, the potential FRGs used for the diagnosis, prognosis and therapy for atherosclerosis are still unclear. We aimed to identify the ferroptosis-related differentially expressed genes (DEGs) of atherosclerosis. We downloaded the mRNA-sequencing data of patients with atherosclerosis from the Gene Expression Omnibus (GEO) database. HMOX1 was identified as an essential ferroptosis-related DEG by bioinformatic analysis of the GSE28829 and GSE43292 datasets. The pro-ferroptotic effect of HMOX1 was validated through cell experiments. Then we conducted a single-gene analysis of HMOX1 and found that high-expression of HMOX1 in atherosclerotic plaques was accompanied by matrix metalloproteinases (MMPs) producing and M0 macrophages infiltration. Taken together, our present study suggested HMOX1 as a potential diagnostic biomarker for atherosclerosis and provided more evidence about the vital role of ferroptosis in atherosclerosis progression.

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Section: Discussionmentioning

confidence: 99%

Identification of HMOX1 as a Critical Ferroptosis-Related Gene in Atherosclerosis

Wang

et al. 2022

Front. Cardiovasc. Med.

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“…As a new mechanism of cell death, the discovery of ferroptosis and the mechanisms involved in its regulation may help to develop novel treatments for several diseases. Recent studies have documented significant effects of ferroptosis on the development and progression of T1DM ( 59 ); T2DM ( 60 , 61 ); gestational diabetes mellitus ( 60 – 62 ); and diabetes complications such as DKD ( 27 ), DCM ( 29 ), DR ( 63 , 64 ), diabetes-induced endothelial dysfunction ( 32 ), cognitive dysfunction ( 31 ), wound healing ( 65 ), diabetic atherosclerosis ( 66 ), and DOP ( 67 ). The molecular mechanisms of ferroptosis in diabetic complications involve multiple proteins, including acyl-CoA synthetase long chain family member 4 (ACSL4), high-mobility group box-1 (HMGB1), hypoxia-inducible factor-1α (HIF-1α), heme oxygenase-1 (HO-1), tripartite motif containing 46 (TRIM46), circ-PSEN1, NCOA4 ( 68 ), and Nox2, and negative genes, Gpx4 , Nrf2 , xCT , adenosine monophosphate-activated protein kinase, heat shock factor 1 ( HSF1 ), and nutrient-deprivation autophagy factor-1 ( NAF-1 ) ( 69 ) ( Figure 2 ).…”

Section: Effects and The Molecular Mechanisms Of Ferroptosis On Diabe...mentioning

confidence: 99%

Ferroptosis as a Novel Therapeutic Target for Diabetes and Its Complications

Yang

2022

Front. Endocrinol.

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The global diabetes epidemic and its complications are increasing, thereby posing a major threat to public health. A comprehensive understanding of diabetes mellitus (DM) and its complications is necessary for the development of effective treatments. Ferroptosis is a newly identified form of programmed cell death caused by the production of reactive oxygen species and an imbalance in iron homeostasis. Increasing evidence suggests that ferroptosis plays a pivotal role in the pathogenesis of diabetes and diabetes-related complications. In this review, we summarize the potential impact and regulatory mechanisms of ferroptosis on diabetes and its complications, as well as inhibitors of ferroptosis in diabetes and diabetic complications. Therefore, understanding the regulatory mechanisms of ferroptosis and developing drugs or agents that target ferroptosis may provide new treatment strategies for patients with diabetes.

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“…Gene interference technologies can also be applied to manage the occurrence and development of diabetes complications. Studies have found that knocking out the Heme oxygenase 1 (Hmox1) gene can reduce iron overload, reactive oxygen species, and lipid peroxidation and inhibit ferroptosis, in turn helping to resist diabetic atherosclerosis [ 68 ]. It has been demonstrated that inhibition of DNA (cytosine-5)-methyltransferase 1 (DNMT-1) can reduce ferroptosis in diabetes myocardial ischemia/reperfusion injury, probably due to the involvement of NCOA4-mediated ferritinophagy.…”

Section: Potential Treatments Targeting Ferroptosis and Ferritinophag...mentioning

confidence: 99%

Ferroptosis and ferritinophagy in diabetes complications

Xia

et al. 2022

Molecular Metabolism

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HMOX1 upregulation promotes ferroptosis in diabetic atherosclerosis

Cited by 95 publications

References 65 publications

Identification of HMOX1 as a Critical Ferroptosis-Related Gene in Atherosclerosis

Identification of HMOX1 as a Critical Ferroptosis-Related Gene in Atherosclerosis

Ferroptosis as a Novel Therapeutic Target for Diabetes and Its Complications

Ferroptosis and ferritinophagy in diabetes complications

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