ArticleCell & bioscience2021
Neurohormonal activation induces intracellular iron deficiency and mitochondrial dysfunction in cardiac cells.
Article in Cell & bioscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Anaemia predicts iron homoeostasis dysregulation and modulates the response to empagliflozin in heart failure with reduced ejection fraction: the EMPATROPISM-FE trial.European heart journal · 2025Trial
- Empagliflozin effects on iron metabolism as a possible mechanism for improved clinical outcomes in non-diabetic patients with systolic heart failure.Nature cardiovascular research · 2023Trial
- Cardiovascular-kidney-metabolic syndrome as a mitochondrial systems disorder.Nature reviews. Nephrology · 2026Review
- The regulation of mitochondrial ferritin on mitochondrial redox balance is essential to cell fate decision.Redox biology · 2026Review
- Iron Matters: Comparative Impact of Beta-Adrenergic Stimulation and Iron Chelation on Cardiac Iron Metabolism and Mitochondrial Function.Biomolecules · 2026Article
- A perspective on the future of heart failure research.Journal of molecular and cellular cardiology plus · 2026Article
- Stress-Induced Dysregulation of Brain Iron Metabolism and Its Links to Neurological Disorders.Biology · 2025Review
- The transcriptional profile of iron deficiency in patients with heart failure: Heme-sparing and reduced immune processes.European journal of heart failure · 2025Article
- Targeting macro- and micro-nutrient regulation of HNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Myocardial Performance Improvement After Iron Replacement in Heart Failure Patients: The IRON-PATH II Echo-Substudy.Journal of clinical medicine · 2025Article
- Iron Deficiency Treatment in Heart Failure-Challenges and Therapeutic Solutions.Journal of clinical medicine · 2025Review
- Association Between Different Insulin Resistance Indices and Heart Failure in US Adults With Diabetes Mellitus.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2024Article
- Identification of three mechanistic pathways for iron-deficient heart failure.European heart journal · 2024Review
- Iron Dyshomeostasis and Mitochondrial Function in the Failing Heart: A Review of the Literature.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2024Review
- Soluble Transferrin Receptor as Iron Deficiency Biomarker: Impact on Exercise Capacity in Heart Failure Patients.Journal of personalized medicine · 2023Article
- Elevated BUN Upon Admission as a Predictor of in-Hospital Mortality Among Patients with Acute Exacerbation of COPD: A Secondary Analysis of Multicenter Cohort Study.International journal of chronic obstructive pulmonary disease · 2023Article
- How can sodium-glucose cotransporter 2 inhibitors stimulate erythrocytosis in patients who are iron-deficient? Implications for understanding iron homeostasis in heart failure.European journal of heart failure · 2022Review
- Clinical and Molecular Aspects of Iron Metabolism in Failing Myocytes.Life (Basel, Switzerland) · 2022Review
- Expression of Iron Metabolism Proteins in Patients with Chronic Heart Failure.Journal of clinical medicine · 2022Article
- Hemosiderin Accumulation in Liver Decreases Iron Availability in Tachycardia-Induced Porcine Congestive Heart Failure Model.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIron deficiency (ID) is common in patients with heart failure (HF) and is associated with poor outcomes, yet its role in the pathophysiology of HF is not well-defined. We sought to determine the consequences of HF neurohormonal activation in iron homeostasis and mitochondrial function in cardiac cells.
methodsHF was induced in C57BL/6 mice by using isoproterenol osmotic pumps and embryonic rat heart-derived H9c2 cells were subsequently challenged with Angiotensin II and/or Norepinephrine. The expression of several genes and proteins related to intracellular iron metabolism were assessed by Real time-PCR and immunoblotting, respectively. The intracellular iron levels were also determined. Mitochondrial function was analyzed by studying the mitochondrial membrane potential, the accumulation of radical oxygen species (ROS) and the adenosine triphosphate (ATP) production.
resultsHearts from isoproterenol-stimulated mice showed a decreased in both mRNA and protein levels of iron regulatory proteins, transferrin receptor 1, ferroportin 1 and hepcidin compared to control mice. Furthermore, mitoferrin 2 and mitochondrial ferritin were also downregulated in the hearts from HF mice. Similar data regarding these key iron regulatory molecules were found in the H9c2 cells challenged with neurohormonal stimuli. Accordingly, a depletion of intracellular iron levels was found in the stimulated cells compared to non-stimulated cells, as well as in the hearts from the isoproterenol-induced HF mice. Finally, neurohormonal activation impaired mitochondrial function as indicated by the accumulation of ROS, the impaired mitochondrial membrane potential and the decrease in the ATP levels in the cardiac cells.
conclusionsHF characteristic neurohormonal activation induced changes in the regulation of key molecules involved in iron homeostasis, reduced intracellular iron levels and impaired mitochondrial function. The current results suggest that iron could be involved in the pathophysiology of HF.
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