The DOI matches its Crossref record; 62 of the 62 references it cites were found in a registry or an index.
ALOX15-launched PUFA-phospholipids peroxidation increases the susceptibility of ferroptosis in ischemia-induced myocardial damage
Open accessAbstract
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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Cited by
Iron Homeostasis and Ferroptosis in Human Diseases: Mechanisms and Therapeutic Prospects
Ru, Q., Li, Y., Chen, L., Wu, Y., Min, J., & Wang, F. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01969-z · Cited by 724
Self-citationTargeting ferroptosis opens new avenues for the development of novel therapeutics
Sun, S., Shen, J., Jiang, J., Wang, F., & Min, J. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01606-1 · Cited by 608
Regulated cell death in myocardial ischemia–reperfusion injury
Xiang, Q., Yi, X., Zhu, X.-H., Wei, X., & Jiang, D.-S. (2024) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2023.10.010 · Cited by 448
Metadata
- Authors
- Ma, X.-H., Liu, J.-H.-Z., Liu, C.-Y., Sun, W.-Y., Duan, W.-J., Wang, G., Kurihara, H., He, R.-R., Li, Y.-F., Chen, Y., & Shang, H.
- Venue
- Signal Transduction and Targeted Therapy
- Published
- 2022-08-15
- Volume
- 7
- Issue
- 1
- Pages
- 288-288
- ISSN
- 2059-3635 (ISSN-L)
- OpenAlex
- W4291901367
- Cited by
- 281
- References
- 62
- FWCI
- 30.72
- Type
- journal article
- Language
- en
- Open access
- gold
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- Ma, X.-H., Liu, J.-H.-Z., Liu, C.-Y., Sun, W.-Y., Duan, W.-J., Wang, G., Kurihara, H., He, R.-R., Li, Y.-F., Chen, Y., & Shang, H. (2022). ALOX15-launched PUFA-phospholipids peroxidation increases the susceptibility of ferroptosis in ischemia-induced myocardial damage. Signal Transduction and Targeted Therapy. https://doi.org/10.1038/s41392-022-01090-z
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