ArticleJournal of the American Heart Association2025
IL1RAP Expression in Human Atherosclerosis: A Target of Novel Antibodies to Reduce Vascular Inflammation and Adhesion.
Article in Journal of the American Heart Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Monotropein mitigates atherosclerotic plaque vulnerability through circ_0140736/miR-495/SIRPα-mediated efferocytosis.iScience · 2026Article
- Single-cell insights into maladaptive endothelial plasticity and therapeutic targets in diabetic vascular complications.Cardiovascular diabetology · 2026Review
- Soybean oil and leucine in late gestation and lactation improve maternal and offspring lipid metabolism and insulin sensitivity: insights from pig model.Frontiers in veterinary science · 2026Article
- Antagonist Binding Actively Disrupts Interleukin-1 Receptor Dynamics to Block Co-receptor Recruitment.Computational and structural biotechnology journal · 2026Article
- Dichotomous roles of IL-36 and IL-38 in cardiovascular disease.Frontiers in immunology · 2025Review
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Authors and funding
10 authors.
Funding
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Abstract
backgroundBlockade of IL1RAP (interleukin 1 receptor associated protein) was recently shown to reduce atherosclerosis in mice, but the effect on human vascular cells is largely unknown. Targeting the IL1RAP coreceptor represents a novel strategy to block the IL1RAP-dependent cytokines IL (interleukin)-1, IL-33, and IL-36. In the present study, we aimed to evaluate the role of novel antibodies targeting IL1RAP to reduce the effects of IL-1β, IL-33, or IL-36γ in human vascular cells.
methodsExpression of IL1RAP was observed in human atherosclerotic plaques by immunohistochemistry and microarray and in endothelial cells by flow cytometry. Endothelial cells were cultured with IL-1β, IL-33, or IL-36γ cytokines with or without IL1RAP antibodies and analyzed with Olink proteomics, ELISA, Western blot, and real-time quantitative polymerase chain reaction. The functional effect of IL1RAP antibodies on endothelial cells were analyzed with adhesion and permeability assays.
resultsOlink proteomics showed inhibition of the inflammatory proteins LIF (leukemia inhibitory factor), OPG (osteoprotegerin), CCL4 (C-C motif chemokine ligand 4), and MCP-3 (monocyte chemoattractant protein 3) by IL1RAP-blockade in endothelial cells after IL-1β stimulation. In addition, the IL1RAP antibodies inhibited IL-1β, and IL-33 induced IL-6 and IL-8 secretion. Secretion of MCP-1 (monocyte chemoattractant protein 1) was induced by IL-1β, IL-33, and IL-36γ, and subsequently was inhibited by IL1RAP antibodies. Similar effects were found on mRNA expression level. Endothelial expression of the adhesion markers
conclusionsIL1RAP-targeting antibodies can reduce the expression of inflammatory cytokines and markers of adhesion in endothelial cells, which may be of importance for future putative targeted treatments against cardiovascular disease.
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