Iron deficiency and cardiovascular disease

Haehling, Stephan von; Jankowska, Ewa A.; Veldhuisen, Dirk J. van; Ponikowski, Piotr; Anker, Stefan D.

doi:10.1038/nrcardio.2015.109

Cited by 251 publications

(177 citation statements)

References 91 publications

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“…Iron is an essential cofactor for a wide range of cellular processes, including various metabolic pathways (such as OxPhos), DNA maintenance, and gene expression (51). Dysfunction of iron homeostasis directly causes a variety of human diseases, including Friedreich's ataxia, and likely contributes to neurodegenerative disease, microbial pathogenesis, various cancers, and cardiovascular disease (52)(53)(54)(55). Despite the known association of iron deficiency with these and other disorders, many of the basic mechanisms regulating cellular adaptation to iron deprivation are unknown.…”

Section: Discussionmentioning

confidence: 99%

Iron Deprivation Induces Transcriptional Regulation of Mitochondrial Biogenesis

Rensvold

Krautkramer

Dowell

et al. 2016

Journal of Biological Chemistry

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Mitochondria are essential organelles that adapt to stress and environmental changes. Among the nutrient signals that affect mitochondrial form and function is iron, whose depletion initiates a rapid and reversible decrease in mitochondrial biogenesis through unclear means. Here we demonstrate that, unlike the canonical iron-induced alterations to transcript stability, loss of iron dampens the transcription of genes encoding mitochondrial proteins with no change to transcript half-life. Using mass spectrometry, we demonstrate that these transcriptional changes are accompanied by dynamic alterations to histone acetylation and methylation levels that are largely reversible upon readministration of iron. Moreover, histone deacetylase inhibition abrogates the decreased histone acetylation observed upon iron deprivation and restores normal transcript levels at genes encoding mitochondrial proteins. Collectively, we demonstrate that deprivation of an essential nutrient induces transcriptional repression of organellar biogenesis involving epigenetic alterations.

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Section: Discussionmentioning

confidence: 99%

Iron Deprivation Induces Transcriptional Regulation of Mitochondrial Biogenesis

Rensvold

Krautkramer

Dowell

et al. 2016

Journal of Biological Chemistry

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“…This results in decreased utilization of O 2 by irondependent mitochondrial enzymes in cardiomyocytes [72], and an increased risk of hospitalization or even of death [70,73]. Of note, IV iron therapy has been shown to be beneficial in CHF patients with ID (see also below) [71,74,75], while a recent trial with oral iron yielded negative results [76]. This refractoriness to oral iron was linked to relatively high (instead of suppressed) hepcidin levels in CHF ID patients [76].…”

Section: Oral Iron Therapy In the Hepcidin Eramentioning

confidence: 99%

“…The best studied condition in this sense is chronic heart failure (CHF), where low-grade chronic inflammation is known to play an important role [69]. ID is quite common in CHF, involving at least 30% of patients [70,71]. Multiple factors concur to determine ID in CHF, including decreased iron intake because of anorexia, malabsorption due to edema of the intestinal mucosa, and, possibly, occult bleeding favored by concomitant assumption of antithrombotic drugs.…”

Section: Oral Iron Therapy In the Hepcidin Eramentioning

confidence: 99%

Modern iron replacement therapy: clinical and pathophysiological insights

et al. 2017

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Iron deficiency, with or without anemia, is extremely frequent worldwide, representing a major public health problem. Iron replacement therapy dates back to the seventeenth century, and has progressed relatively slowly until recently. Both oral and intravenous traditional iron formulations are known to be far from ideal, mainly because of tolerability and safety issues, respectively. At the beginning of this century, the discovery of hepcidin/ferroportin axis has represented a turning point in the knowledge of the pathophysiology of iron metabolism disorders, ushering a new era. In the meantime, advances in the pharmaceutical technologies are producing newer iron formulations aimed at minimizing the problems inherent with traditional approaches. The pharmacokinetic of oral and parenteral iron is substantially different, and diversities have become even clearer in light of the hepcidin master role in regulating systemic iron homeostasis. Here we review how iron therapy is changing because of such important advances in both pathophysiology and pharmacology.

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“…The effects of iron deficiency on patients with cardiac disease therefore go far beyond any reduction in oxygen supply but may contribute to directly to worsening cardiac or skeletal muscle function (Von Haehling et al, 2015).…”

Section: Pathophysiology Of Iron Deficiency In the Failing Heartmentioning

confidence: 99%

Investigation and treatment for iron deficiency in heart failure: the unmet need in Lower and Middle Income Countries

Makubi

Roberts

2017

Br J Haematol

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Summary Frank iron deficiency has been associated with a wide range of cardiac and pulmonary abnormalities including non‐ischaemic cardiomyopathy. Iron deficiency anaemia and isolated iron deficiency are well‐defined adverse prognostic factors in non‐ischaemic cardiac failure. Furthermore, iron‐deficient patients in chronic heart failure with a serum ferritin of <100 μg/l or <300 μg/l with reduced transferrin saturation of <20%, who were given intravenous iron showed improved clinical outcomes. Iron deficiency with or without anaemia affects over a quarter of the world's population, but the impact of iron deficiency in heart failure and the effective management of iron deficiency in heart failure in Lower and Middle Income Countries (LMICs) is not well described. Heart failure in African cohorts occurs at a younger age than in North America and Europe and is more likely to be due to hypertension. Recent studies suggest that iron deficiency anaemia, which is very common in heart failure patients in Africa, and iron deficiency are independently associated with a poor prognosis in heart failure. Preliminary data suggest that iron deficiency in patients with heart failure can be treated with oral iron, with significant beneficial effects on haematological and physiological variables. Cost may prohibit the use of intravenous iron on a large scale in LMICs and optimal regimes to treat iron deficiency in heart failure patients with oral iron therapy remain to be defined.

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Iron deficiency and cardiovascular disease

Cited by 251 publications

References 91 publications

Iron Deprivation Induces Transcriptional Regulation of Mitochondrial Biogenesis

Iron Deprivation Induces Transcriptional Regulation of Mitochondrial Biogenesis

Modern iron replacement therapy: clinical and pathophysiological insights

Investigation and treatment for iron deficiency in heart failure: the unmet need in Lower and Middle Income Countries

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