Balance of cardiac and systemic hepcidin and its role in heart physiology and pathology

Vela, Driton

doi:10.1038/labinvest.2017.111

Cited by 36 publications

(26 citation statements)

References 117 publications

(198 reference statements)

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“…Dietary non-heme iron (Fe 3+ ) absorption is improved by acidic pH and mainly occurs in the proximal duodenum by divalent metal ion transporter 1 (DMT1), after being reduced by duodenal cytochrome b to Fe 2+ [4,67]. On the contrary, heme iron Fe 2+ , an important source for both the human and the intestinal microbiota, is directly absorbed by heme/folate transporter 1 (HCP1) in the host and by siderophores like enterobactin in bacteria.…”

Section: Ironmentioning

confidence: 99%

Thyroid-Gut-Axis: How Does the Microbiota Influence Thyroid Function?

et al. 2020

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A healthy gut microbiota not only has beneficial effects on the activity of the immune system, but also on thyroid function. Thyroid and intestinal diseases prevalently coexist—Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) are the most common autoimmune thyroid diseases (AITD) and often co-occur with Celiac Disease (CD) and Non-celiac wheat sensitivity (NCWS). This can be explained by the damaged intestinal barrier and the following increase of intestinal permeability, allowing antigens to pass more easily and activate the immune system or cross-react with extraintestinal tissues, respectively. Dysbiosis has not only been found in AITDs, but has also been reported in thyroid carcinoma, in which an increased number of carcinogenic and inflammatory bacterial strains were observed. Additionally, the composition of the gut microbiota has an influence on the availability of essential micronutrients for the thyroid gland. Iodine, iron, and copper are crucial for thyroid hormone synthesis, selenium and zinc are needed for converting T4 to T3, and vitamin D assists in regulating the immune response. Those micronutrients are often found to be deficient in AITDs, resulting in malfunctioning of the thyroid. Bariatric surgery can lead to an inadequate absorption of these nutrients and further implicates changes in thyroid stimulating hormone (TSH) and T3 levels. Supplementation of probiotics showed beneficial effects on thyroid hormones and thyroid function in general. A literature research was performed to examine the interplay between gut microbiota and thyroid disorders that should be considered when treating patients suffering from thyroid diseases. Multifactorial therapeutic and preventive management strategies could be established and more specifically adjusted to patients, depending on their gut bacteria composition. Future well-powered human studies are warranted to evaluate the impact of alterations in gut microbiota on thyroid function and diseases.

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Section: Ironmentioning

confidence: 99%

Thyroid-Gut-Axis: How Does the Microbiota Influence Thyroid Function?

et al. 2020

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“…Surprisingly, hepcidin is also expressed in other tissues, such as heart [37], kidney [38], brain [39] and placenta [40]. The exact role of this locally produced hepcidin is still unclear; however, there is some evidence that it may be associated with tissue-specific iron regulation [4, 41].…”

Section: Cardiac-specific Iron Deficiencymentioning

confidence: 99%

Structural and functional abnormalities in iron-depleted heart

et al. 2018

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Iron deficiency (ID) is a common and ominous comorbidity in heart failure (HF) and predicts worse outcomes, independently of the presence of anaemia. Accumulated data from animal models of systemic ID suggest that ID is associated with several functional and structural abnormalities of the heart. However, the exact role of myocardial iron deficiency irrespective of systemic ID and/or anaemia has been elusive. Recently, several transgenic models of cardiac-specific ID have been developed to investigate the influence of ID on cardiac tissue. In this review, we discuss structural and functional cardiac consequences of ID in these models and summarize data from clinical studies. Moreover, the beneficial effects of intravenous iron supplementation are specified.

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“…At systemic level, circulating HAMP is synthesized by the liver, where it is induced in iron overloading conditions and is inhibited by iron deficiency due to anemia, hypoxia, ineffective erythropoiesis, and inflammation [10, 11]. HAMP is also expressed in the heart, brain, kidney, and placenta [15]; in these tissues, its role is less defined, but it is likely involved in iron handling. HAMP expression is regulated by different members of the TGF- β superfamily, including BMP (bone morphogenetic protein) receptors, associated BMP ligands, and the cytoplasmic SMAD transcription factor [16].…”

Section: Introductionmentioning

confidence: 99%

New Insights into the Hepcidin-Ferroportin Axis and Iron Homeostasis in iPSC-Derived Cardiomyocytes from Friedreich’s Ataxia Patient

Bolotta

Abruzzo

Baldassarro

et al. 2019

Oxidative Medicine and Cellular Longevity

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Iron homeostasis in the cardiac tissue as well as the involvement of the hepcidin-ferroportin (HAMP-FPN) axis in this process and in cardiac functionality are not fully understood. Imbalance of iron homeostasis occurs in several cardiac diseases, including iron-overload cardiomyopathies such as Friedreich’s ataxia (FRDA, OMIM no. 229300), a hereditary neurodegenerative disorder. Exploiting the induced pluripotent stem cells (iPSCs) technology and the iPSC capacity to differentiate into specific cell types, we derived cardiomyocytes of a FRDA patient and of a healthy control subject in order to study the cardiac iron homeostasis and the HAMP-FPN axis. Both CTR and FRDA iPSCs-derived cardiomyocytes express cardiac differentiation markers; in addition, FRDA cardiomyocytes maintain the FRDA-like phenotype. We found that FRDA cardiomyocytes show an increase in the protein expression of HAMP and FPN. Moreover, immunofluorescence analysis revealed for the first time an unexpected nuclear localization of FPN in both CTR and FRDA cardiomyocytes. However, the amount of the nuclear FPN was less in FRDA cardiomyocytes than in controls. These and other data suggest that iron handling and the HAMP-FPN axis regulation in FRDA cardiac cells are hampered and that FPN may have new, still not fully understood, functions. These findings underline the complexity of the cardiac iron homeostasis.

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Balance of cardiac and systemic hepcidin and its role in heart physiology and pathology

Cited by 36 publications

References 117 publications

Thyroid-Gut-Axis: How Does the Microbiota Influence Thyroid Function?

Thyroid-Gut-Axis: How Does the Microbiota Influence Thyroid Function?

Structural and functional abnormalities in iron-depleted heart

New Insights into the Hepcidin-Ferroportin Axis and Iron Homeostasis in iPSC-Derived Cardiomyocytes from Friedreich’s Ataxia Patient

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