ArticleBlood2015
Oxidized LDL activates blood platelets through CD36/NOX2-mediated inhibition of the cGMP/protein kinase G signaling cascade.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 2 of them syntheses that pooled it.
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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.
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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.
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Who cites it
98 citing papers in PubMed, 2 syntheses or guidelines pooled it, 170 citations in OpenAlex.
- Effects of statin therapy on mean platelet volume in patients with risk of cardiovascular diseases: a systematic review and meta-analysis.Bioscience reports · 2019Pooled it
- The use of platelet indices, plateletcrit, mean platelet volume and platelet distribution width in emergency non-traumatic abdominal surgery: a systematic review.Biochemia medica · 2016Pooled it
- Associations of blood donor and product characteristics with platelet transfusion outcomes.Blood advances · 2026Article
- Apolipoprotein D, a Novel Ligand for CD36, Is Essential for Blood-Brain Barrier Integrity.Circulation · 2026Article
- TNIK as a molecular switch regulating platelet function in hemostasis and hyperlipidemia-associated thrombosis.Blood advances · 2026Article
- Effect of the atherogenic index of plasma on the expression of platelet CD36 and CD62P in patients with acute ischemic stroke: a retrospective study from Tianjin, China.BMC neurology · 2026Article
- Platelet Membrane Receptors and Signalling Pathways.Handbook of experimental pharmacology · 2026Review
- The immune receptor FcRγ-chain mediates CD36-induced platelet activation and thrombosis by oxidized low-density lipoproteins.Blood advances · 2025Article
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- NADPH oxidase 2 inhibitor GSK2795039 exerts antiplatelet and antithrombotic activity.Scientific reports · 2025Article
- NOX-NOS crosstalk in the liver-brain axis: Novel insights for redox regulation and neurodegenerative diseases.Redox biology · 2025Review
- Butyrate Produced by Gut Microbiota Regulates Atherosclerosis: A Narrative Review of the Latest Findings.International journal of molecular sciences · 2025Review
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- Antiplatelet Effects of DMPC-Based Synthetic High-Density Lipoproteins: Exploring Particle Structure and Noncholesterol Efflux Mechanisms.Molecular pharmaceutics · 2025Article
- PCSK9 in Vascular Aging and Age-Related Diseases.Aging and disease · 2025Review
- Association of statin use with 28-day mortality in the Medical Information Mart for Intensive Care IV database: a retrospective cohort study.Journal of thoracic disease · 2025Article
- Sulforaphane attenuates aldose reductase-mediated platelet dysfunction in high glucose-stimulated human platelets via downregulation of the Src/ROS/p53 signaling pathway.Frontiers in nutrition · 2025Article
- Exploring the Pleiotropy of PCSK9: A Wide Range of Influences from Lipid Regulation to Extrahepatic Function.Journal of inflammation research · 2025Review
- Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Oxidized low-density lipoprotein (oxLDL) promotes unregulated platelet activation in dyslipidemic disorders. Although oxLDL stimulates activatory signaling, it is unclear how these events drive accelerated thrombosis. Here, we describe a mechanism for oxLDL-mediated platelet hyperactivity that requires generation of reactive oxygen species (ROS). Under arterial flow, oxLDL triggered sustained generation of platelet intracellular ROS, which was blocked by CD36 inhibitors, mimicked by CD36-specific oxidized phospholipids, and ablated in CD36(-/-) murine platelets. oxLDL-induced ROS generation was blocked by the reduced NAD phosphate oxidase 2 (NOX2) inhibitor, gp91ds-tat, and absent in NOX2(-/-) mice. The synthesis of ROS by oxLDL/CD36 required Src-family kinases and protein kinase C (PKC)-dependent phosphorylation and activation of NOX2. In functional assays, oxLDL abolished guanosine 3',5'-cyclic monophosphate (cGMP)-mediated signaling and inhibited platelet aggregation and arrest under flow. This was prevented by either pharmacologic inhibition of NOX2 in human platelets or genetic ablation of NOX2 in murine platelets. Platelets from hyperlipidemic mice were also found to have a diminished sensitivity to cGMP when tested ex vivo, a phenotype that was corrected by infusion of gp91ds-tat into the mice. This study demonstrates that oxLDL and hyperlipidemia stimulate the generation of NOX2-derived ROS through a CD36-PKC pathway and may promote platelet hyperactivity through modulation of cGMP signaling.
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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.