ArticleCirculation research2024
Ferroptosis-Mediated Inflammation Promotes Pulmonary Hypertension.
Article in Circulation research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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The trial behind it
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Who cites it
48 citing papers in PubMed.
- From Retina to Vasculature: Oxidative Stress as a Common Mechanistic Link Between Age-Related Macular Degeneration and Cardiovascular Disease.Antioxidants (Basel, Switzerland) · 2026Review
- Vestitol Ameliorates Ferroptosis-Associated Features and Osteoarthritis Progression Through Modulation of the GSK3B/Nrf2/GPX4 Pathway.Cell biochemistry and biophysics · 2026Article
- Deltex E3 ubiquitin ligase 2 prevents sepsis-induced myocardial injury through degrading TfR1 via promoting K27-linked ubiquitination.Cell death and differentiation · 2026Article
- Ferroptosis in skeletal muscle: from molecular mechanisms to therapeutic interventions.Journal of orthopaedic translation · 2026Review
- Pulmonary Hypertension Molecular Switch: HIF Signaling Pathway.Pulmonary circulation · 2026Review
- Impaired Lung BCAA Metabolism Promotes Ferroptosis and Resultant Pulmonary Arterial Hypertension-Associated Hepatopathy.JACC. Basic to translational science · 2026Article
- Emerging Roles for Metabolism in Myocardial Inflammation During Heart Failure.Immunological reviews · 2026Review
- The Iron Lung: Ferroptosis and Iron Regulation in Aging and Lung Diseases.Physiology (Bethesda, Md.) · 2026Review
- Metabolic Reprogramming-Driven Cardiovascular Immune Damage: From Glyco-Lipotoxicity and Epigenetic Memory to Multidimensional Cross-Organ Communication Networks.International journal of molecular sciences · 2026Review
- The N‑Glycoproteomic Landscape of the Lung in Monocrotaline-Induced Pulmonary Arterial Hypertension.ACS omega · 2026Article
- SMAD7 Downregulation Promotes Ferroptosis in Pulmonary Arterial Hypertension Via the TGF-β1-SMAD2/3 Pathway.Shock (Augusta, Ga.) · 2026Article
- Identification of RUNX1 as a Biomarker for Right Ventricular Remodeling in Pulmonary Arterial Hypertension Using WGCNA.Pulmonary circulation · 2026Article
- Regulated Cell Death in Idiopathic Pulmonary Fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Therapeutic Effects of Active Compounds fromACS omega · 2026Article
- Ketone Ester Attenuates Thoracic Aortic Aneurysm and Dissection by Suppressing Ferroptosis.Cells · 2026Article
- Angiotensin II Disrupts Axo-Axonal Interaction-Mediated Vasorelaxation in Basilar Arteries of Normotensive and Hypertensive Rats.Biomedicines · 2026Article
- Advances in the pathogenesis and clinical management of pulmonary hypertension.Medical review (2021) · 2026Review
- Palmitoylation-Mediated Ubiquitination of SRPK1 Regulates Ferroptosis in High-Fat-Induced Erectile Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- KIF11 prevents retinal endothelial ferroptosis in familial exudative vitreoretinopathy by inhibiting phosphorylation-driven PRDX1 phase separation.Nature communications · 2026Article
- Paradigm shift: from pulmonary vasodilation to cardiopulmonary dual-track therapy-a comprehensive review of pathophysiology and advances in pulmonary hypertension-associated right heart failure.Respiratory research · 2026Review
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
backgroundMitochondrial dysfunction, characterized by impaired lipid metabolism and heightened reactive oxygen species generation, results in lipid peroxidation and ferroptosis. Ferroptosis is an inflammatory mode of cell death that promotes complement activation and macrophage recruitment. In pulmonary arterial hypertension (PAH), pulmonary arterial endothelial cells exhibit cellular phenotypes that promote ferroptosis. Moreover, there is ectopic complement deposition and inflammatory macrophage accumulation in the pulmonary vasculature. However, the effects of ferroptosis inhibition on these pathogenic mechanisms and the cellular landscape of the pulmonary vasculature are incompletely defined.
methodsMultiomics and physiological analyses evaluated how ferroptosis inhibition-modulated preclinical PAH. The impact of adeno-associated virus 1-mediated expression of the proferroptotic protein ACSL (acyl-CoA synthetase long-chain family member) 4 on PAH was determined, and a genetic association study in humans further probed the relationship between ferroptosis and pulmonary hypertension.
resultsFerrostatin-1, a small-molecule ferroptosis inhibitor, mitigated PAH severity in monocrotaline rats. RNA-sequencing and proteomics analyses demonstrated ferroptosis was associated with PAH severity. RNA-sequencing, proteomics, and confocal microscopy revealed complement activation and proinflammatory cytokines/chemokines were suppressed by ferrostatin-1. In addition, ferrostatin-1 combatted changes in endothelial, smooth muscle, and interstitial macrophage abundance and gene activation patterns as revealed by deconvolution RNA-sequencing. Ferroptotic pulmonary arterial endothelial cell damage-associated molecular patterns restructured the transcriptomic signature and mitochondrial morphology, promoted the proliferation of pulmonary artery smooth muscle cells, and created a proinflammatory phenotype in monocytes in vitro. Adeno-associated virus 1-
conclusionsFerroptosis promotes PAH through metabolic and inflammatory mechanisms in the pulmonary vasculature.
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Registered trials
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