The role of hepcidin and iron homeostasis in atherosclerosis

Wunderer, Florian; Traeger, Lisa; Sigurslid, Haakon H.; Meybohm, Patrick; Bloch, Donald B.; Malhotra, Rajeev

doi:10.1016/j.phrs.2020.104664

Cited by 76 publications

(51 citation statements)

References 152 publications

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“…What merits attention is that the endothelial cell-secreted exosome has proven to throw a wrench in the glucocorticoid-induced osteoporosis process by abating ferritinophagy (Yang et al, 2021). Dysregulation of iron homeostasis and metabolism is substantiated to have a close connection to diverse metabolic diseases, such as diabetes (Dubey et al, 2020), obesity, metabolic syndrome (Gonzalez-Dominguez et al, 2020), osteoporosis (Che et al, 2020;Sato et al, 2020) and AS (Wunderer et al, 2020). Thereby, we forecast that the link between exosome and iron metastasis in ferroptosis may be a heated discussion in the near future.…”

Section: Labile Iron Pool-powerful Strength Of the Elder Wandmentioning

confidence: 99%

Ferroptosis and Its Potential Role in Metabolic Diseases: A Curse or Revitalization?

Duan

Lin

et al. 2021

Front. Cell Dev. Biol.

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Ferroptosis is classified as an iron-dependent form of regulated cell death (RCD) attributed to the accumulation of lipid hydroperoxides and redox imbalance. In recent years, accumulating researches have suggested that ferroptosis may play a vital role in the development of diverse metabolic diseases, for example, diabetes and its complications (e.g., diabetic nephropathy, diabetic cardiomyopathy, diabetic myocardial ischemia/reperfusion injury and atherosclerosis [AS]), metabolic bone disease and adrenal injury. However, the specific physiopathological mechanism and precise therapeutic effect is still not clear. In this review, we summarized recent advances about the development of ferroptosis, focused on its potential character as the therapeutic target in metabolic diseases, and put forward our insights on this topic, largely to offer some help to forecast further directions.

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Section: Labile Iron Pool-powerful Strength Of the Elder Wandmentioning

confidence: 99%

Ferroptosis and Its Potential Role in Metabolic Diseases: A Curse or Revitalization?

Duan

Lin

et al. 2021

Front. Cell Dev. Biol.

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“…However, despite this increased knowledge, iron levels and related clinical markers of iron metabolism are not yet routinely measured in sepsis patients and such measurements would also appear to be warranted. In particular, patients with underlying diseases are at increased risk of sepsis-related complications: dysregulated iron metabolism with elevated plasma and/or increased intracellular iron stores is a feature of both, diabetes (Altamura et al 2017 ) and cardiovascular disease (Wunderer et al 2020 ), and has also been implicated in hypertension (Sangartit et al 2016 ).…”

Section: Iron In Systemic Inflammation and Sepsismentioning

confidence: 99%

Iron-withdrawing anti-infectives for new host-directed therapies based on iron dependence, the Achilles’ heel of antibiotic-resistant microbes

Holbein

Ang²,

Allan³

et al. 2021

Environ Chem Lett

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“…Collectively, these findings indicate that the interactions between hepcidin, retained iron, and accumulated lipids are critical for the atherosclerotic role of macrophages. The dual action of macrophage iron depletion in atherosclerosis suggests a potential beneficial effect at early stages of atherosclerosis—associated with improved lipid handling—and detrimental effect in more advanced stages, when intraplaque neovascularization, hemorrhages, and hypoxia occur ( 52 , 89 , 240 ).…”

Section: Current Molecular Mechanisms Of Iron-mediated Vasculotoxicitymentioning

confidence: 99%

Non-Transferrin-Bound Iron in the Spotlight: Novel Mechanistic Insights into the Vasculotoxic and Atherosclerotic Effect of Iron

Vinchi

2021

Antioxidants & Redox Signaling

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Significance: While atherosclerosis is an almost inevitable consequence of aging, food preferences, lack of exercise, and other aspects of the lifestyle in many countries, the identification of new risk factors is of increasing importance to tackle a disease, which has become a major health burden for billions of people. Iron has long been suspected to promote the development of atherosclerosis, but data have been conflicting, and the contribution of iron is still debated controversially. Recent Advances: Several experimental and clinical studies have been recently published about this longstanding controversial problem, highlighting the critical need to unravel the complexity behind this topic. Critical Issues: The aim of the current review is to provide an overview of the current knowledge about the proatherosclerotic impact of iron, and discuss the emerging role of non-transferrin-bound iron (NTBI) as driver of vasculotoxicity and atherosclerosis. Finally, I will provide detailed mechanistic insights on the cellular processes and molecular pathways underlying iron-exacerbated atherosclerosis. Overall, this review highlights a complex framework where NTBI acts at multiple levels in atherosclerosis by altering the serum and vascular microenvironment in a proatherogenic and proinflammatory manner, affecting the functionality and survival of vascular cells, promoting foam cell formation and inducing angiogenesis, calcification, and plaque destabilization. Future Directions: The use of additional iron markers ( e.g. , NTBI) may help adequately predict predisposition to cardiovascular disease. Clinical studies are needed in the aging population to address the atherogenic role of iron fluctuations within physiological limits and the therapeutic value of iron restriction approaches. Antioxid. Redox Signal. 35, 387–414.

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The role of hepcidin and iron homeostasis in atherosclerosis

Cited by 76 publications

References 152 publications

Ferroptosis and Its Potential Role in Metabolic Diseases: A Curse or Revitalization?

Ferroptosis and Its Potential Role in Metabolic Diseases: A Curse or Revitalization?

Iron-withdrawing anti-infectives for new host-directed therapies based on iron dependence, the Achilles’ heel of antibiotic-resistant microbes

Non-Transferrin-Bound Iron in the Spotlight: Novel Mechanistic Insights into the Vasculotoxic and Atherosclerotic Effect of Iron

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