SLC7A11/xCT Prevents Cardiac Hypertrophy by Inhibiting Ferroptosis

Zhang, Xiyu; Zheng, Cuiting; Gao, Zhen; Chen, Hongyu; Li, Kai; Wang, Lingling; Zheng, Yuanyuan; Li, Chunjia; Zhang, Hongjia; Gong, Ming; Zhang, Hongbing; Meng, Yan

doi:10.1007/s10557-021-07220-z

Cited by 67 publications

(39 citation statements)

References 39 publications

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“…Increased cardiac NADPH oxidase 4 expression and decreased cardiac GPX4 activity in animal models after either aortic banding or isoprenaline administration suggest that ROS production and ferroptosis might participate in the progression from compensated hypertrophy to heart failure 209 , 210 . In mice, genetic deletion of the key ferroptosis regulator SLC7A11 was found to exacerbate angiotensin II-mediated cardiac fibrosis, hypertrophy and dysfunction, providing genetic evidence of the involvement of ferroptosis in hypertrophic cardiomyopathy 129 .…”

Section: Ferroptosis In Cardiovascular Diseasementioning

confidence: 94%

“…Moreover, our research group has shown that overexpressing Slc7a11 selectively in cardiomyocytes increases cellular glutathione levels and prevents ferritin H deficiency-mediated cardiac ferroptosis, providing the first evidence that SLC7A11 has an anti-ferroptotic role in the heart 27 . In addition, knocking out Slc7a11 aggravates cardiac hypertrophy and dysfunction in mice, both of which can be reversed by inhibiting ferroptosis 129 .…”

Section: Molecular and Metabolic Drivers Of Ferroptosismentioning

confidence: 99%

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The molecular and metabolic landscape of iron and ferroptosis in cardiovascular disease

et al. 2022

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The maintenance of iron homeostasis is essential for proper cardiac function. A growing body of evidence suggests that iron imbalance is the common denominator in many subtypes of cardiovascular disease. In the past 10 years, ferroptosis, an iron-dependent form of regulated cell death, has become increasingly recognized as an important process that mediates the pathogenesis and progression of numerous cardiovascular diseases, including atherosclerosis, drug-induced heart failure, myocardial ischaemia–reperfusion injury, sepsis-induced cardiomyopathy, arrhythmia and diabetic cardiomyopathy. Therefore, a thorough understanding of the mechanisms involved in the regulation of iron metabolism and ferroptosis in cardiomyocytes might lead to improvements in disease management. In this Review, we summarize the relationship between the metabolic and molecular pathways of iron signalling and ferroptosis in the context of cardiovascular disease. We also discuss the potential targets of ferroptosis in the treatment of cardiovascular disease and describe the current limitations and future directions of these novel treatment targets.

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Section: Ferroptosis In Cardiovascular Diseasementioning

confidence: 94%

Section: Molecular and Metabolic Drivers Of Ferroptosismentioning

confidence: 99%

The molecular and metabolic landscape of iron and ferroptosis in cardiovascular disease

et al. 2022

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“…91 SLC7A11 gene-encoded plasma membrane xCT is identified as a cardioprotective factor in cardiac hypertrophic diseases, since xCT alleviates angiotensin II-induced cardiac fibrosis and pathological cardiac remodeling by inhibiting ferroptosis. 92 Many studies have shown that ferroptosis occurs in myocardial infarction, myocardial IRI, and heart failure, all of which can lead to the formation of fibrosis. 87 GPX4 is significantly downregulated at the transcriptional level in the early and middle stages of myocardial infarction, which results in the accumulation of lipid peroxide and subsequently ferroptosis in cardiomyocytes.…”

Section: Dovepressmentioning

confidence: 99%

Role of Ferroptosis in Fibrotic Diseases

Zhou¹,

Yuan²,

Wang³

et al. 2022

JIR

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Ferroptosis is a unique and pervasive form of regulated cell death driven by iron-dependent phospholipid peroxidation. It results from disturbed cellular metabolism and imbalanced redox homeostasis and is regulated by various cellular metabolic pathways. Recent preclinical studies have revealed that ferroptosis may be an attractive therapeutic target in fibrotic diseases, such as liver fibrosis, pulmonary fibrosis, kidney fibrosis, and myocardial fibrosis. This review summarizes the latest knowledge on the regulatory mechanism of ferroptosis and its roles in fibrotic diseases. These updates may provide a novel perspective for the treatment of fibrotic diseases as well as future research.

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“…For histological analysis, heart tissues obtained from experimental animals were fixed, embedded and sectioned into 5-μm thick slices as described previously. 26 Sections were stained with Masson's trichrome (collagen, blue; cytoplasm, red/pink) for collagen deposition analysis. Sections were stained with wheat germ agglutinin (WGA) to assess cellular hypertrophy.…”

Section: Histopathology Analysismentioning

confidence: 99%

“…Neonatal rat cardiac myocytes were isolated as previously described. 26,36 Hearts obtained from 1-to 2-day-old neonatal rat hearts were digested by trypsin and collagenase II. The dissociated cells in dulbecco's modified eagles medium (DMEM)/F-12 medium with 10% fetal bovine serum (FBS) and 1% penicillin and streptomycin were plated in a 5% CO 2 incubator for 90 minutes.…”

Section: Primary Cell Culture and Treatmentmentioning

confidence: 99%

Sulfasalazine exacerbates angiotensin II‐induced cardiac remodelling by activating Akt signal pathway

Chen

Zheng

Gao

et al. 2022

Clin Exp Pharma Physio

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A thorough understanding of the pathological process underlying hypertensioninduced cardiac remodelling may help in prevention and treatment of heart failure.Angiotensin II (AngII) results in cardiac fibrosis and hypertrophy partly through activation of inflammation, which increases the fibroblasts and promotes extracellular matrix production. Sulfasalazine (SASP) has evident anti-inflammatory effects and pharmacological functions on autoimmune disease. The roles of SASP in the cardiac remodelling remain unknown. In this study, we established AngII-induced cardiac remodelling mice model and then treated with SASP. Blood pressure, cardiac pump function and pathological changes of cardiac remodelling were analysed in these mice. To explore the mechanism, phosphorylated Akt was detected in vivo and vitro. In this study, we found that SASP aggravated cardiac dysfunction, hypertrophy and fibrosis after AngII infusion. In addition, SASP activated Akt in AngII-remodelled mouse hearts and cardiac cells. Our findings indicate that independent of anti-inflammatory property, SASP exacerbates AngII-induced cardiac remodelling by activation of Akt signalling pathway.

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SLC7A11/xCT Prevents Cardiac Hypertrophy by Inhibiting Ferroptosis

Cited by 67 publications

References 39 publications

The molecular and metabolic landscape of iron and ferroptosis in cardiovascular disease

The molecular and metabolic landscape of iron and ferroptosis in cardiovascular disease

Role of Ferroptosis in Fibrotic Diseases

Sulfasalazine exacerbates angiotensin II‐induced cardiac remodelling by activating Akt signal pathway

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