ArticleSignal transduction and targeted therapy2022
ALOX15-launched PUFA-phospholipids peroxidation increases the susceptibility of ferroptosis in ischemia-induced myocardial damage.
Article in Signal transduction and targeted therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers, 1 of them a synthesis that pooled it.
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Who cites it
149 citing papers in PubMed, 1 synthesis or guideline pooled it, 251 citations in OpenAlex.
- Pharmacological mechanisms of traditional Chinese medicine in treating gastric cancer: a focus on the ferroptosis regulation.Frontiers in pharmacology · 2025Pooled it
- Nrf2 de-SUMOylation alleviates myocardial ischemia-reperfusion injury (MIRI) by attenuating myocardial ferroptosis in mice.Redox report : communications in free radical research · 2026Article
- A molecular modeling and machine learning-based approach for the identification of potential human ALOX15 inhibitors.Journal of molecular modeling · 2026Article
- ABHD11-Mediated mtDNA Transcription Restored Mitochondrial Function to Attenuate Cardiomyocyte Ferroptosis After Myocardial Infarction.Circulation · 2026Article
- Luteolin Attenuates Hypoxia-Induced Ferroptosis in Human Brain Microvascular Endothelial Cells Through Modulation of the PPARγ/FABP5/ALOX15 Signaling Pathway.Biomedicines · 2026Article
- Light-Controlled Modulation of 15-Lipoxygenase-1 Regulates Intestinal Inflammatory Signaling.Angewandte Chemie (International ed. in English) · 2026Article
- Silencing arachidonate 15-lipoxygenase alleviates hypoxia-induced cognitive impairment through the mediation of phospholipase A2 group IVC-LPC18:0 to suppress ferroptosis.Molecular biomedicine · 2026Article
- WTAP Histone Lactylation Drives the YTHDF1/ALOX15 Axis to Regulate Ferroptosis in Myocardial Ischemia-Reperfusion Injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Eicosapentaenoic acid ethyl ester, cardiac metabolomic and lipidomic signatures, and cardioprotection in myocardial infarction.European heart journal · 2026Article
- Dual-Metal Regulation of Cardiac Remodeling: Targeting the LOXL2-Ferroptosis Axis in Metal-Induced Cardiac Dysfunction.Cardiovascular toxicology · 2026Review
- Serum GPX4, ALOX15, and FPN1 are associated with severity of carotid atherosclerosis: a cross-sectional observational study.BMC neurology · 2026Observational
- Regulated cell death plasticity in cancer: thresholds, reversibility, and therapeutic failure.Journal of translational medicine · 2026Review
- Article
- Potential Relationship Between Ferroptosis and Pyroptosis in Myocardial Ischemia/Reperfusion Injury: Molecular Mechanisms and Therapeutic Targets.Reviews in cardiovascular medicine · 2026Review
- Ferroptosis-related proteins ALOX15 and HMOX1 are upregulated and associated with inflammation in patients with diabetic nephropathy: a prospective cross-sectional study.International urology and nephrology · 2026Article
- Metabolic Mechanisms of Hexavalent Chromium-Induced Splenic Immune Injury via Oxidative Stress and Ferroptosis Pathways in New Zealand Rabbits.Metabolites · 2026Article
- Targeting Ferroptosis and Pyroptosis in Cardiovascular Diseases: Mechanisms and Therapeutic Implication.Journal of cardiovascular translational research · 2026Review
- Arachidonate lipoxygenase 5 metabolism axis promoting ferroptosis: a potential druggable target for doxorubicin-induced cardiomyopathy.British journal of cancer · 2026Article
- A therapeutic relay strategy enabled by spatiotemporally programmable nanoplatforms for multilayered cardioprotection against MI/RI.Journal of nanobiotechnology · 2026Article
- Research Progress on the Role of Traditional Chinese Medicine in Regulating Ferroptosis in Cardiovascular Diseases.Biology · 2026Review
89 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Myocardial ischemia/reperfusion (I/R) injury is a classic type of cardiovascular disease characterized by injury to cardiomyocytes leading to various forms of cell death. It is believed that irreversible myocardial damage resulted from I/R occurs due to oxidative stress evoked during the reperfusion phase. Here we demonstrate that ischemia triggers a specific redox reaction of polyunsaturated fatty acids (PUFA)-phospholipids in myocardial cells, which acts as a priming signaling that initiates the outbreak of robust oxidative damage in the reperfusion phase. Using animal and in vitro models, the crucial lipid species in I/R injury were identified to be oxidized PUFAs enriched phosphatidylethanolamines. Using multi-omics, arachidonic acid 15-lipoxygenase-1 (ALOX15) was identified as the primary mediator of ischemia-provoked phospholipid peroxidation, which was further confirmed using chemogenetic approaches. Collectively, our results reveal that ALOX15 induction in the ischemia phase acts as a "burning point" to ignite phospholipid oxidization into ferroptotic signals. This finding characterizes a novel molecular mechanism for myocardial ischemia injury and offers a potential therapeutic target for early intervention of I/R injury.
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