ArticleBlood2013
Platelet hyperreactivity explains the bleeding abnormality and macrothrombocytopenia in a murine model of sitosterolemia.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 62 citations in OpenAlex.
- Ezetimibe reduces plant sterol accumulation and favorably increases platelet count in sitosterolemia.The Journal of pediatrics · 2015Trial
- Factors Affecting Circulating Phytosterol Levels: Toward an Integrated Understanding of Atherogenicity and Atheroprotection by Dietary and Circulating Phytosterols.Current atherosclerosis reports · 2025Review
- From Bernard-Soulier syndrome to sitosterolemia: the role of genetic analysis in bleeding diathesis.Thrombosis journal · 2025Article
- Homozygous phytosterolemia and a literature review: A case report.World journal of clinical cases · 2025Article
- The disturbance of ABC transporters in patients with dengue fever: integration of metabolomics and transcriptomics.Frontiers in cellular and infection microbiology · 2025Article
- From Xanthomas to Genetic Diagnosis: A Case Report of Sitosterolemia in an Infant with a Homozygous ABCG5 c.1166G>A (p.Arg389His) Variant.Clinical, cosmetic and investigational dermatology · 2025Article
- Dietary phytosterols induce infertility in female mice via epigenomic modulations.Communications biology · 2024Article
- Platelet proteomic profiling in sitosterolemia suggests thrombocytopenia is driven by lipid disorder and not platelet aberrations.Blood advances · 2024Article
- [Child with sitosterolemia initially presenting with hemolytic anemia and thrombocytopenia: a case repore and literrature review].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2024Article
- Hemolytic anemia and macrothrombocytopenia: A lipid problem?American journal of hematology · 2023Article
- Phytosterols and Cardiovascular Risk Evaluated against the Background of Phytosterolemia Cases-A German Expert Panel Statement.Nutrients · 2023Article
- Clinical characteristics of sitosterolemic children with xanthomas as the first manifestation.Lipids in health and disease · 2022Article
- The impact of aberrant von Willebrand factor-GPIbα interaction on megakaryopoiesis and platelets in humanized type 2B von Willebrand disease model mouse.Haematologica · 2022Article
- Cucurbitacins Elicit Anti-Platelet Activity via Perturbation of the Cytoskeleton and Integrin Function.Thrombosis and haemostasis · 2022Article
- Clinical and Genetic Analysis of a Family With Sitosterolemia Caused by a Novel ATP-Binding Cassette Subfamily G Member 5 Compound Heterozygous Mutation.Frontiers in cardiovascular medicine · 2022Article
- Diagnosis and Management of Sitosterolemia 2021.Journal of atherosclerosis and thrombosis · 2021Review
- Sitosterolemia: Twenty Years of Discovery of the Function ofInternational journal of molecular sciences · 2021Review
- Sitosterolemia: Four Cases of an Uncommon Cause of Hemolytic Anemia (Mediterranean Stomatocytosis with Macrothrombocytopenia).Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2021Article
- Case Report: Next Generation Sequencing in Clinical Practice-A Real Tool for Ending the Protracted Diagnostic Odyssey.Frontiers in cardiovascular medicine · 2021Article
- Inherited thrombocytopenias: history, advances and perspectives.Haematologica · 2020Review
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5 authors at 3 institutions in 2 countries.
Funding
Abstract
Sitosterolemia is a rare, autosomal recessive disease caused by mutations in the adenosine triphosphate-binding cassette transporter genes ABCG5 or ABCG8 that result in accumulation of xenosterols in the body. Clinical manifestations include tendon xanthomas, premature coronary artery disease, hemolytic anemia, macrothrombocytopenia, and bleeding. Although the effect of sterol accumulation on the predisposition for atherosclerosis is evident, how xenosterol accumulation leads to defects in platelet physiology is unknown. Sitosterolemia induced in Abcg5- and Abcg8-deficient mice fed a high plant sterol diet resulted in accumulation of free sterols in platelet plasma membranes, leading to hyperactivatable platelets characterized by constitutive binding of fibrinogen to its αIIbβ3 integrin receptor, internalization of the αIIbβ3 complex, generation of platelet-derived microparticles, and changes in the quantity and subcellular localization of filamin. The latter was associated with macrothrombocytopenia, shedding of GPIbα, impaired platelet adhesion to von Willebrand factor, and inability to form stable thrombi. Plasma levels of soluble GPIbα were strongly correlated with plasma sitosterol levels in samples from human sitosterolemic patients, implicating a similar mechanism of sterol-induced platelet passivation in the human disease. Intercalation of plant sterols into the plasma membrane therefore results in dysregulation of multiple platelet activation pathways, leading to macrothrombocytopenia and bleeding.
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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.