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

Huang, Fangze; Yang, Ronghua; Xiao, Zezhou; Xie, Yong; Lin, Xuefeng; Zhu, Peng; Zhou, Pengyu; Lu, Jun; Zheng, Shaoyi

doi:10.3389/fcell.2021.737971

Cited by 30 publications

(36 citation statements)

References 140 publications

(214 reference statements)

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“…Iron level alterations are detrimental in both directions as proved by the poor prognosis of heart failure patients with commonly associated iron deficiency [ 132 ]. Accordingly, iron mishandling has been proposed to be a major trigger for severe injury to cardiomyocytes and hepatocytes and therefore an important player in developing heart and liver failure [ 55 , 133 ]. On the other hand, while iron overload has been demonstrated as being associated with several cardiac diseases, its essential role in mediating ischemic preconditioning cardioprotection has been proposed [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, iron mishandling has been proposed to be a major trigger for severe injury to cardiomyocytes and hepatocytes and therefore an important player in developing heart and liver failure [ 55 , 133 ]. On the other hand, while iron overload has been demonstrated as being associated with several cardiac diseases, its essential role in mediating ischemic preconditioning cardioprotection has been proposed [ 55 ]. These reports are in accordance with studies demonstrating the double role of ROS in mediating both injury and protection to the heart, ROS production being strictly related to iron activity inside the cell [ 134 ].…”

Section: Discussionmentioning

confidence: 99%

Section: Ferroptosis In Heart Failurementioning

confidence: 99%

“…Numerous cardiovascular diseases are characterized by cardiac and vascular cell loss trough necrosis, apoptosis, and autophagy. As a novel type cell death, ferroptosis has been reported to play a pivotal role in the onset and development of various cardiovascular diseases mediated by an accumulation of lethal lipid hydroperoxides triggered by iron [ 55 ]. In the heart, several mechanisms are critical for the triggering of ferroptosis, including iron metabolism, glutamine metabolism, and lipid peroxidation, while recent studies suggest that myocardial dysfunction induced by ferroptosis can be inhibited by iron chelators and antioxidants [ 56 ].…”

Section: Ferroptosis In Heart Failurementioning

confidence: 99%

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Iron Overload, Oxidative Stress, and Ferroptosis in the Failing Heart and Liver

et al. 2021

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Iron accumulation is a key mediator of several cytotoxic mechanisms leading to the impairment of redox homeostasis and cellular death. Iron overload is often associated with haematological diseases which require regular blood transfusion/phlebotomy, and it represents a common complication in thalassaemic patients. Major damages predominantly occur in the liver and the heart, leading to a specific form of cell death recently named ferroptosis. Different from apoptosis, necrosis, and autophagy, ferroptosis is strictly dependent on iron and reactive oxygen species, with a dysregulation of mitochondrial structure/function. Susceptibility to ferroptosis is dependent on intracellular antioxidant capacity and varies according to the different cell types. Chemotherapy-induced cardiotoxicity has been proven to be mediated predominantly by iron accumulation and ferroptosis, whereas there is evidence about the role of ferritin in protecting cardiomyocytes from ferroptosis and consequent heart failure. Another paradigmatic organ for transfusion-associated complication due to iron overload is the liver, in which the role of ferroptosis is yet to be elucidated. Some studies report a role of ferroptosis in the initiation of hepatic inflammation processes while others provide evidence about an involvement in several pathologies including immune-related hepatitis and acute liver failure. In this manuscript, we aim to review the literature to address putative common features between the response to ferroptosis in the heart and liver. A better comprehension of (dys)similarities is pivotal for the development of future therapeutic strategies that can be designed to specifically target this type of cell death in an attempt to minimize iron-overload effects in specific organs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Ferroptosis In Heart Failurementioning

confidence: 99%

Section: Ferroptosis In Heart Failurementioning

confidence: 99%

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Iron Overload, Oxidative Stress, and Ferroptosis in the Failing Heart and Liver

et al. 2021

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“…Mechanistically, erastin triggers ferroptosis either by combining mitochondrial VDAC2/3 to disrupt the respiratory chain together with ROS accumulation or weakening Xc system activity to attenuate GSH concentration accompanied by GPX4 inactivation ( Yagoda et al, 2007 ; Yang et al, 2014 ). RSL3, impervious to the upstream of GPX4 including GSH depletion and cysteine intussuscepts, is able to inactivate GPX4 by the binding protein site, in turn augmenting ROS generation to initiate ferroptosis ( Huang et al, 2021 ). On account of the succedaneous antioxidant approach upregulated by blocking GSH synthesis, BSO, owning perciclular capacity in suppressing peripheral GSH biosynthesis and eventually inactivating GPX4 to induce ferroptosis, exhibits lower efficacy on occasioning ferroptosis-related chain reaction than RSL3 ( Harris et al, 2015 ).…”

Section: Initiators and Inhibitors Of Ferroptosis As The Potential Targets For Mirimentioning

confidence: 99%

A Novel Insight Into the Fate of Cardiomyocytes in Ischemia-Reperfusion Injury: From Iron Metabolism to Ferroptosis

Liu

Yao

et al. 2021

Front. Cell Dev. Biol.

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Ischemia-reperfusion injury (IRI), critically involved in the pathology of reperfusion therapy for myocardial infarction, is closely related to oxidative stress the inflammatory response, and disturbances in energy metabolism. Emerging evidence shows that metabolic imbalances of iron participate in the pathophysiological process of cardiomyocyte IRI [also termed as myocardial ischemia-reperfusion injury (MIRI)]. Iron is an essential mineral required for vital physiological functions, including cellular respiration, lipid and oxygen metabolism, and protein synthesis. Nevertheless, cardiomyocyte homeostasis and viability are inclined to be jeopardized by iron-induced toxicity under pathological conditions, which is defined as ferroptosis. Upon the occurrence of IRI, excessive iron is transported into cells that drive cardiomyocytes more vulnerable to ferroptosis by the accumulation of reactive oxygen species (ROS) through Fenton reaction and Haber–Weiss reaction. The increased ROS production in ferroptosis correspondingly leads cardiomyocytes to become more sensitive to oxidative stress under the exposure of excess iron. Therefore, ferroptosis might play an important role in the pathogenic progression of MIRI, and precisely targeting ferroptosis mechanisms may be a promising therapeutic option to revert myocardial remodeling. Notably, targeting inhibitors are expected to prevent MIRI deterioration by suppressing cardiomyocyte ferroptosis. Here, we review the pathophysiological alterations from iron homeostasis to ferroptosis together with potential pathways regarding ferroptosis secondary to cardiovascular IRI. We also provide a comprehensive analysis of ferroptosis inhibitors and initiators, as well as regulatory genes involved in the setting of MIRI.

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The association between ferroptosis and autophagy in cardiovascular diseases

Zhang,

Yang,

Ouyang

et al. 2024

Cell Biochemistry & Function

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Autophagy is a process in which cells degrade intracellular substances and play a variety of roles in cells, such as maintaining intracellular homeostasis, preventing cell overgrowth, and removing pathogens. It is highly conserved during the evolution of eukaryotic cells. So far, the study of autophagy is still a hot topic in the field of cytology. Ferroptosis is an iron‐dependent form of cell death, accompanied by the accumulation of reactive oxygen species and lipid peroxides. With the deepening of research, it has been found that ferroptosis, like autophagy, is involved in the occurrence and development of cardiovascular diseases. The relationship between autophagy and ferroptosis is complex, and the association between the two in cardiovascular disease remains to be clarified. This article reviews the mechanism of autophagy and ferroptosis and their correlation, and discusses the relationship between them in cardiovascular diseases, which is expected to provide new and important treatment strategies for cardiovascular diseases.

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

Cited by 30 publications

References 140 publications

Iron Overload, Oxidative Stress, and Ferroptosis in the Failing Heart and Liver

Iron Overload, Oxidative Stress, and Ferroptosis in the Failing Heart and Liver

A Novel Insight Into the Fate of Cardiomyocytes in Ischemia-Reperfusion Injury: From Iron Metabolism to Ferroptosis

The association between ferroptosis and autophagy in cardiovascular diseases

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