Ferroptosis Is a Potential Novel Diagnostic and Therapeutic Target for Patients With Cardiomyopathy

Zhai, Zhenyu; Zou, Pengtao; Liu, Fuxiang; Xia, Zirong; Li, Juxiang

doi:10.3389/fcell.2021.649045

Cited by 19 publications

(15 citation statements)

References 166 publications

(154 reference statements)

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“…In addition, ferroptosis is closely related to iron metabolism under iron overload. Ferroptosis, as a kind of programmed apoptosis, is characterized by excessive accumulation of lipid peroxides and reactive oxygen species ( Zhai et al, 2021 ). Ferroptosis, often accompanied with iron overload, caused the tissue damage mainly driven by iron overload and lipid peroxidation.…”

Section: Iron Overload: An Imbalance Iron Metabolism That Causes Chronic and Common Diseasesmentioning

confidence: 99%

Role of Flavonoids in the Treatment of Iron Overload

Wang

et al. 2021

Front. Cell Dev. Biol.

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Iron overload, a high risk factor for many diseases, is seen in almost all human chronic and common diseases. Iron chelating agents are often used for treatment but, at present, most of these have a narrow scope of application, obvious side effects, and other disadvantages. Recent studies have shown that flavonoids can affect iron status, reduce iron deposition, and inhibit the lipid peroxidation process caused by iron overload. Therefore, flavonoids with iron chelating and antioxidant activities may become potential complementary therapies. In this study, we not only reviewed the research progress of iron overload and the regulation mechanism of flavonoids, but also studied the structural basis and potential mechanism of their function. In addition, the advantages and disadvantages of flavonoids as plant iron chelating agents are discussed to provide a foundation for the prevention and treatment of iron homeostasis disorders using flavonoids.

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Section: Iron Overload: An Imbalance Iron Metabolism That Causes Chronic and Common Diseasesmentioning

confidence: 99%

Role of Flavonoids in the Treatment of Iron Overload

Wang

et al. 2021

Front. Cell Dev. Biol.

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“…The occurrence of ferroptosis relies on enormous cellular iron and lipid hydroperoxide, which subsequently induce overwhelming lipid accumulation in cells and interfere with the homeostasis of redox reactions, thus promoting cell death ( Xie et al, 2016 ; Dixon, 2017 ; Stockwell et al, 2017 ; Zhai et al, 2021 ). Ferroptosis can initiate the Fenton reaction and other peroxidation with excessive iron, which can convert the product of mitochondrial oxidative respiration, hydrogen peroxide, into hydroxyl-free radical under the catalysis of ferrous ion.…”

Section: Overview Of Ferroptosismentioning

confidence: 99%

“…Furthermore, lipid peroxidation spontaneously produces PLOO⋅ and PLO⋅, which constantly recruit lipid molecules to free radical reactions and form a lipid peroxidation circle ( Davies and Guo, 2014 ). It is believed that Fenton reaction can also provide the free radicals for lipid peroxidation metabolism, which can be a connecting point between iron metabolism and lipid peroxidation in ferroptosis ( Zhai et al, 2021 ).…”

Section: Mechanism Of Ferroptosismentioning

confidence: 99%

“…However, the molecular mechanisms of ferroptotic cell death in cardiomyocytes remain unclear. Except for the destruction of iron metabolism, GSH depletion and lipid peroxidation, various pathways are also involved in the process of ferroptosis, such as high levels of extracellular glutamic acid, organelle-mediated pathways, Nrf2 pathway and so on ( Zhai et al, 2021 ). Moreover, there are few researches on the relationship between ferroptosis and pathogenesis of arrhythmia.…”

Section: Perspective and Conclusionmentioning

confidence: 99%

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Targeting Ferroptosis to Treat Cardiovascular Diseases: A New Continent to Be Explored

Huang

Yang

Xiao

et al. 2021

Front. Cell Dev. Biol.

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Cardiovascular diseases, including cardiomyopathy, myocardial infarction, myocardial ischemia/reperfusion injury, heart failure, vascular injury, stroke, and arrhythmia, are correlated with cardiac and vascular cell death. Ferroptosis is a novel form of non-apoptotic regulated cell death which is characterized by an iron-driven accumulation of lethal lipid hydroperoxides. The initiation and execution of ferroptosis are under the control of several mechanisms, including iron metabolism, glutamine metabolism, and lipid peroxidation. Recently, emerging evidence has demonstrated that ferroptosis can play an essential role in the development of various cardiovascular diseases. Recent researches have shown the ferroptosis inhibitors, iron chelators, genetic manipulations, and antioxidants can alleviate myocardial injury by blocking ferroptosis pathway. In this review, we systematically described the mechanisms of ferroptosis and discussed the role of ferroptosis as a novel therapeutic strategy in the treatment of cardiovascular diseases.

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“…Upon MI, GSH was depleted in cardiomyocytes and gradually increased oxidative stress, leading to accumulation of glutathione disulphide (GSSG), an oxidized form of GSH [49]. A recent report showed that pathological conditions such as MI-induced heart failure cause intracellular GSH depletion [50] and lead to ferroptosis [17,42].…”

Section: Cardioprotective Effects Of Histochrome On Myocardial I/r Injurymentioning

confidence: 99%

Histochrome Attenuates Myocardial Ischemia-Reperfusion Injury by Inhibiting Ferroptosis-Induced Cardiomyocyte Death

Hwang

Park

et al. 2021

Antioxidants

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Reactive oxygen species (ROS) and intracellular iron levels are critical modulators of lipid peroxidation that trigger iron-dependent non-apoptotic ferroptosis in myocardial ischemia-reperfusion (I/R) injury. Histochrome (HC), with a potent antioxidant moiety and iron-chelating capacity, is now available in clinical practice. However, limited data are available about the protective effects of HC on ferroptotic cell death in myocardial I/R injury. In this study, we investigated whether the intravenous administration of HC (1 mg/kg) prior to reperfusion could decrease myocardial damage by reducing ferroptosis. Rats undergoing 60 min of ischemia and reperfusion were randomly divided into three groups as follows: (1) Sham, (2) I/R control, and (3) I/R + HC. Serial echocardiography up to four weeks after I/R injury showed that intravenous injection of HC significantly improved cardiac function compared to the I/R controls. In addition, the hearts of rats who received intravenous injection of HC exhibited significantly lower cardiac fibrosis and higher capillary density. HC treatment decreased intracellular and mitochondrial ROS levels by upregulating the expression of nuclear factor erythroid 2-related factor (Nrf2) and its downstream genes. HC also inhibited erastin- and RSL3-induced ferroptosis in rat neonatal cardiomyocytes by maintaining the intracellular glutathione level and through upregulated activity of glutathione peroxidase 4. These findings suggest that early intervention with HC before reperfusion rescued myocardium from I/R injury by preventing ferroptotic cell death. Therefore, HC is a promising therapeutic option to provide secondary cardioprotection in patients who undergo coronary reperfusion therapy.

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Ferroptosis Is a Potential Novel Diagnostic and Therapeutic Target for Patients With Cardiomyopathy

Cited by 19 publications

References 166 publications

Role of Flavonoids in the Treatment of Iron Overload

Role of Flavonoids in the Treatment of Iron Overload

Targeting Ferroptosis to Treat Cardiovascular Diseases: A New Continent to Be Explored

Histochrome Attenuates Myocardial Ischemia-Reperfusion Injury by Inhibiting Ferroptosis-Induced Cardiomyocyte Death

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