Iron deficiency defined as depleted body iron stores and unmet cellular iron requirements is common in AHF, and identifies those with the poor outcome. Its correction may be an attractive therapeutic approach.

Skeletal and respiratory myopathy not only constitutes an important pathophysiological feature of heart failure and chronic obstructive pulmonary disease, but also contributes to debilitating symptomatology and predicts worse outcomes in these patients. Accumulated evidence from laboratory experiments, animal models, and interventional studies in sports medicine suggests that undisturbed systemic iron homeostasis significantly contributes to the effective functioning of skeletal muscles. In this review, we discuss the role of iron status for the functioning of skeletal muscle tissue, and highlight iron deficiency as an emerging therapeutic target in chronic diseases accompanied by a marked muscle dysfunction.

Specific skeletal myopathy constitutes a common feature of heart failure, chronic obstructive pulmonary disease, and type 2 diabetes mellitus, where it can be characterized by the loss of skeletal muscle oxidative capacity. There is evidence from in vitro and animal studies that iron deficiency affects skeletal muscle functioning mainly in the context of its energetics by limiting oxidative metabolism in favour of glycolysis and by alterations in both carbohydrate and fat catabolic processing. In this review, we depict the possible molecular pathomechanisms of skeletal muscle energetic impairment and postulate iron deficiency as an important factor causally linked to loss of muscle oxidative capacity that contributes to skeletal myopathy seen in patients with heart failure, chronic obstructive pulmonary disease, and type 2 diabetes mellitus.

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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The differential availability of iron during hypoxia is presumed to affect the functioning of cardiac and skeletal myocytes. Rat H9C2 cardiomyocytes and L6G8C5 myocytes were cultured for 48 h in normoxic or hypoxic conditions at the optimal, reduced or increased iron concentration. The mRNA expression levels of markers of apoptosis [B‑cell lymphoma‑2 (Bcl2; inhibition) and Bcl‑2‑activated X protein (Bax; induction)], atrophy (Atrogin), glycolysis (pyruvate kinase 2; PKM2) and iron metabolism [transferrin receptor 1 (TfR1; iron importer), ferroportin 1 (FPN1; iron exporter), ferritin heavy chain (FTH; iron storage protein) and hepcidin (HAMP; iron regulator)] were determined using reverse transcription‑quantitative polymerase chain reaction, and cell viability was measured using an tetrazolium reduction assay. Cardiomyocytes and myocytes, when exposed to hypoxia, demonstrated an increased Bax/Bcl‑2 gene expression ratio (P<0.05). Additional deferoxamine (DFO) treatment resulted in further increases in Bax/Bcl‑2 in each cell type (P<0.001 each) and this was associated with the 15% loss in viability. The analogous alterations were observed in both cell types upon ammonium ferric citrate (AFC) treatment during hypoxia; however, the increased Bax/Bcl‑2 ratio and associated viability loss was lower compared with that in case of DFO treatment (P<0.05 each). Under hypoxic conditions, myocytes demonstrated an increased expression of PKM2 (P<0.01). Additional DFO treatment caused an increase in the mRNA expression levels of PKM2 and Atrogin‑1 (P<0.001 and P<0.05, respectively), whereas AFC treatment caused an increased mRNA expression of PKM2 (P<0.01) and accompanied decreased mRNA expression of Atrogin‑1 (P<0.05). The expression augmentation of PKM2 during hypoxia was greater upon low iron compared with that of ferric salt treatment (P<0.01). Both cell types upon DFO during hypoxia demonstrated the increased expression of TfR1 and HAMP (all P<0.05), which was associated with the increased Bax/Bcl‑2 ratio (all R>0.6 and P<0.05). In conclusion, during hypoxia iron deficiency impairs the viability of cardiomyocytes and myocytes more severely compared with iron excess. In myocytes, during hypoxia iron may act in a protective manner, since the level of atrophy is decreased in the iron‑salt‑treated cells.

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Background: Proinflammatory activation and autoimmune processes underlie the pathophysiology of hidradenitis suppurativa (HS). Iron deficiency (ID) is frequently present in inflammation-mediated chronic diseases, irrespective of anemia. Objectives: We aimed to characterize iron status in patients with HS. Methods: Serum concentrations of ferritin, transferrin saturation (Tsat), soluble transferrin receptor and hepcidin were assessed as the biomarkers of iron status in 74 patients with HS and 44 healthy subjects. ID was defined as ferritin <100 µg/L or ferritin 100–299 µg/L with Tsat <20% (following the definition used in the other studies in chronic disease). Results: Compared with controls, patients with HS demonstrated a deranged iron status as evidenced by decreased levels of ferritin (91 ± 87 vs. 157 ± 99 µg/L), Tsat (21.5 ± 10.8 vs. 42.2 ± 11.7%) and hepcidin (31.3 ± 25.9 vs. 44.2 ± 22.0 ng/mL) (all p < 0.05 vs. controls). There was also a trend toward higher values of soluble transferrin receptor (1.23 ± 0.35 vs. 1.12 ± 0.19 mg/L) (p = 0.09 vs. controls). Disease severity (assessed with the Hidradenitis Suppurativa Severity Index and the 3-degree Hurley scale) did not differentiate iron status biomarkers. ID was present in 75% of HS patients, and its prevalence was not related with disease severity (Hurley I/II/III – 82 vs. 73 vs. 67%). In HS, none of the iron status biomarkers correlated with the levels of interleukin-6 (a marker of proinflammatory activation). Conclusions: The majority of HS patients demonstrate derangements in iron status typical of ID. These abnormalities are neither related to proinflammatory activation nor associated with disease severity. Whether it may have a therapeutic impact needs to be further studied.