ArticleJournal of advanced research2025
Macrophage P2Y12 regulates iron transport and its inhibition protects against atherosclerosis.
Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Cell-Type-Specific Regulation of Ferroptosis in Atherosclerosis: Mechanisms and Therapeutic Potential of Natural Products.Cell biochemistry and function · 2026Review
- Ferroptosis-driven immune remodeling in heart failure: the central role of macrophage reprogramming and impaired efferocytosis.Journal of nanobiotechnology · 2026Review
- Review
- Ferroptosis in Vascular Diseases: A Mechanistic and Immunological Perspective on Therapeutic Targeting.Antioxidants (Basel, Switzerland) · 2026Review
- Macrophages in post-chemoradiotherapy hematopoietic injury: a double-edged sword.Cell communication and signaling : CCS · 2026Review
- A Brief Description of the Cellular Mechanisms Involved in Cardiac Chemical Hypoxia.Cardiovascular toxicology · 2026Review
- Discovery and Evaluation of Novel Calenduloside E Derivatives Targeting HSP90β in Ox-LDL-Induced HUVECs Injury.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Novel Duck Orthoreovirus Induces Ferroptosis in HD11 Cells by Hijacking Cellular Iron Metabolism and Promoting Iron Accumulation.Transboundary and emerging diseases · 2026Article
- Ferroptosis of Macrophages and Endothelial Cells in Atherosclerosis: Molecular Mechanisms and Therapeutic Targets.Reviews in cardiovascular medicine · 2025Review
- Current status and challenges of multi-omics research using animal models of atherosclerosis.Journal of molecular and cellular cardiology plus · 2025Review
- GDF15 attenuates myocardial hypoxic injury by inhibiting mitochondrial damage through BNIP3 pathway.Molecular biology reports · 2025Article
- Crosstalk between ferroptosis and NLRP3, a possible therapeutic target in experimentally-induced rheumatoid arthritis: role of P2Y12R inhibition in modulating P53/SLC7A11/ALOX15 signaling.Inflammopharmacology · 2025Article
- IKZF1 exacerbates the inflammatory response by epigenetically modulating mitochondrial function following acute peritonitis.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionIron retention is commonly observed in atherosclerotic plaques and is believed to be detrimental to atherosclerosis. Platelet P2Y12 is a target of antiplatelet therapy in preventing thrombotic complications of atherosclerosis. The protective effect of P2Y12 on hematopoiesis reported by our previous work implies the involvement of P2Y12 in iron metabolism.
objectivesThis study further investigated the role of P2Y12 in the iron metabolism of macrophages, the key player in systemic iron homeostasis and atherosclerosis.
methodsThe association between serum iron and the use of P2Y12 inhibitors was evaluated by a case-control study in human. Secondary iron overload and atherosclerosis animal models were established in P2Y12-deficient zebrafish to explore the role of P2Y12 in macrophage iron metabolism in vivo. Both iron-overloaded murine primary peritoneal macrophages (PMs) and ox-LDL-treated PMs with P2Y12 knockdown were used for in vitro studies. RNA sequencing and pharmacological approaches were performed to investigate the downstream mechanisms.
resultsIncreased serum iron level was positively associated with P2Y12 inhibitor usage [odds ratio (OR) = 10.333 (1.281-83.370)]. Elevated serum iron level and transferrin saturation, reduced hepatic and splenic iron content, and decreased iron staining in macrophages were observed in secondary iron overload P2Y12-deficient zebrafish. Deficiency of P2Y12 in ApoEb
conclusionP2Y12 inhibition decreased hepcidin autocrine through repressing NF-κB p65 phosphorylation in macrophages, preventing intracellular iron retention and atherosclerosis.
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