ArticleJournal of the American College of Cardiology2013
Heme levels are increased in human failing hearts.
Article in Journal of the American College of Cardiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 79 citations in OpenAlex.
- Impact of iron deficiency on left ventricular noninvasive myocardial work indices in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation.Cardiology journal · 2026Article
- The transcriptional profile of iron deficiency in patients with heart failure: Heme-sparing and reduced immune processes.European journal of heart failure · 2025Article
- Decoding IBD progression: a dynamic biomarker atlas for personalized disease stratification.Journal of translational medicine · 2025Article
- Anthracycline-induced cardiomyopathy in childhood cancer survivors is associated with gene signatures of mitochondrial dysfunction-a COG ALTE03N1 report.Cardio-oncology (London, England) · 2025Article
- An erythroid-specific lentiviral vector improves anemia and iron metabolism in a new model of XLSA.Blood · 2025Article
- Iron Metabolism in Cardiovascular Disease.Advances in experimental medicine and biology · 2025Review
- 25-Hydroxycholecalciferol Improves Cardiac Metabolic Adaption, Mitochondrial Biogenetics, and Redox Status to Ameliorate Pathological Remodeling and Functional Failure in Obese Chickens.Antioxidants (Basel, Switzerland) · 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
- Role of Erythropoiesis-Stimulating Agents in Cardiovascular Protection in CKD Patients: Reappraisal of Their Impact and Mechanisms.Cardiovascular drugs and therapy · 2023Review
- METTL3-modified lncRNA-SNHG8 binds to PTBP1 to regulate ALAS2 expression to increase oxidative stress and promote myocardial infarction.Molecular and cellular biochemistry · 2023Article
- Iron Metabolism in Cardiovascular Disease: Physiology, Mechanisms, and Therapeutic Targets.Circulation research · 2023Review
- Dysregulation of Iron Metabolism-Linked Genes at Myocardial Tissue and Cell Levels in Dilated Cardiomyopathy.International journal of molecular sciences · 2023Article
- Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients.Open medicine (Warsaw, Poland) · 2023Review
- Succinyl-CoA-based energy metabolism dysfunction in chronic heart failure.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Fuel source shift or cost reduction: Context-dependent adaptation strategies in closely relatedZoological research · 2022Article
- Micronutrient deficiencies in heart failure: Mitochondrial dysfunction as a common pathophysiological mechanism?Journal of internal medicine · 2022Review
- Joint efficacy of the three biomarkers SNCA, GYPB and HBG1 for atrial fibrillation and stroke: Analysis via the support vector machine neural network.Journal of cellular and molecular medicine · 2022Article
- Iron Deficiency in Heart Failure: Mechanisms and Pathophysiology.Journal of clinical medicine · 2021Review
- Kidney toxicity of the BRAF-kinase inhibitor vemurafenib is driven by off-target ferrochelatase inhibition.Kidney international · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
objectivesThe goal of this study was to characterize the regulation of heme and non-heme iron in human failing hearts.
backgroundIron is an essential molecule for cellular physiology, but in excess it facilitates oxidative stress. Mitochondria are the key regulators of iron homeostasis through heme and iron-sulfur cluster synthesis. Because mitochondrial function is depressed in failing hearts and iron accumulation can lead to oxidative stress, we hypothesized that iron regulation may also be impaired in heart failure (HF).
methodsWe measured mitochondrial and cytosolic heme and non-heme iron levels in failing human hearts retrieved during cardiac transplantation surgery. In addition, we examined the expression of genes regulating cellular iron homeostasis, the heme biosynthetic pathway, and micro-RNAs that may potentially target iron regulatory networks.
resultsAlthough cytosolic non-heme iron levels were reduced in HF, mitochondrial iron content was maintained. Moreover, we observed a significant increase in heme levels in failing hearts, with corresponding feedback inhibition of the heme synthetic enzymes and no change in heme degradation. The rate-limiting enzyme in heme synthesis, delta-aminolevulinic acid synthase 2 (ALAS2), was significantly upregulated in HF. Overexpression of ALAS2 in H9c2 cardiac myoblasts resulted in increased heme levels, and hypoxia and erythropoietin treatment increased heme production through upregulation of ALAS2. Finally, increased heme levels in cardiac myoblasts were associated with excess production of reactive oxygen species and cell death, suggesting a maladaptive role for increased heme in HF.
conclusionsDespite global mitochondrial dysfunction, heme levels are maintained above baseline in human failing hearts.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.