ArticleMolecular medicine (Cambridge, Mass.)2025
12/15-lipoxygenase mediates disturbed flow-induced endothelial dysfunction and atherosclerosis.
Article in Molecular medicine (Cambridge, Mass.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
3 citing papers in PubMed.
- Serum GPX4, ALOX15, and FPN1 are associated with severity of carotid atherosclerosis: a cross-sectional observational study.BMC neurology · 2026Observational
- Neutrophil Irgm1 ameliorates sepsis-induced myocardial dysfunction by promoting Alox15 degradation.Redox biology · 2026Article
- Allosteric properties of mammalian ALOX15 orthologs.The Journal of biological chemistry · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
backgroundDisturbed flow regions in the vasculature are predisposed to endothelial dysfunction and atherosclerotic plaque formation. The enzyme 12/15-lipoxygenase (12/15-LOX, encoded by ALOX15) has emerged as a promising therapeutic target for atherosclerosis. However, the relationship between 12/15-LOX and disturbed flow-induced atherosclerosis remains uncharacterized.
methodsExpression of 12/15-LOX in endothelial cells (ECs) exposed to steady flow and disturbed flow was compared in vivo and in vitro. The effect of 12/15-LOX on ECs was analyzed by using ALOX15 knockout mice, EC-specific adeno-associated virus (AAV)-mediated delivery of ALOX15-shRNA, and specific inhibitors. Partial carotid ligation mouse model was established to ascertain the role of 12/15-LOX in ECs under disturbed flow.
resultsCompared to steady flow regions, 12/15-LOX was significantly upregulated in ECs at disturbed flow sites. In vivo and in vitro experiments demonstrated that 12/15-LOX promoted disturbed flow-elicited endothelial dysfunction. Mass spectrometry analysis revealed that 12/15-LOX promoted production of 15 s-HETE, a pro-inflammatory eicosanoid metabolite, in ECs exposed to disturbed flow. Furthermore, we showed that disturbed flow activated 12/15-LOX expression through transactivation of its promoter by a mechanosensitive transcription factor sterol regulatory element binding protein 2 (SREBP2). Finally, EC-specific knockdown or inhibition of 12/15-LOX substantially attenuated the development of atherosclerosis in disturbed flow regions.
conclusionsDisturbed flow promoted 12/15-LOX expression via SREBP2, thereby leading to increased pro-inflammatory PUFA metabolites and ECs dysfunction. Targeting at SREBP2-12/15-LOX pathway should provide therapeutic perspectives to attenuate disturbed flow-induced atherosclerosis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.