ArticleBlood2015
Circulating cell membrane microparticles transfer heme to endothelial cells and trigger vasoocclusions in sickle cell disease.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers.
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Who cites it
153 citing papers in PubMed, 247 citations in OpenAlex.
- Effects of repleting organic phosphates in banked erythrocytes on plasma metabolites and vasoactive mediators after red cell exchange transfusion in sickle cell disease.Blood transfusion = Trasfusione del sangue · 2020Trial
- Association Between Nitric Oxide, Oxidative Stress, Eryptosis, Red Blood Cell Microparticles, and Vascular Function in Sickle Cell Anemia.Frontiers in immunology · 2020Trial
- Trial
- Thrombocytosis and the generation of platelet-derived microparticles in the pathophysiology of sickle cell disease.British journal of haematology · 2026Review
- Case Report: Coexisting Hereditary Spherocytosis, Limited Cutaneous Systemic Sclerosis, and Antiphospholipid Syndrome: A Rare Autoimmune-Hemolytic Association.International journal of rheumatic diseases · 2026Article
- Sickle cell disease-associated pulmonary hypertension: an integrated framework linking pathologies, mechanisms, and clinical phenotypes.EBioMedicine · 2026Review
- Extracellular Vesicles as Drivers of Lung Endothelial Dysfunction in ARDS: Mechanisms and Therapeutic Opportunities.Comprehensive Physiology · 2026Review
- Review
- Extracellular Vesicles as Mediators of Endothelial and Tubular Injury in Cardiac Surgery-Associated Acute Kidney Injury.Biomedicines · 2026Review
- A cell-nonautonomous heme acquisition pathway enables erythroid hemoglobinization under stress.Science (New York, N.Y.) · 2026Article
- [Treatment practice and outcomes in 125 patients with autoimmune hemolytic anemia: a single-center retrospective analysis].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026Article
- Proangiogenic Properties of Extracellular Vesicles Secreted by Endothelial Cells Reversibly Primed for Anoikis: A Possible Autocrine Mechanism Induced by Astrocytoma Extracellular Matrix.International journal of molecular sciences · 2026Article
- A cell-nonautonomous heme acquisition pathway enables erythroid hemoglobinization under stress.bioRxiv : the preprint server for biology · 2026Article
- High thrombotic burden in severe Chinese wAIHA patients: a single-center retrospective study.Thrombosis journal · 2026Article
- Editorial: Unraveling inflammatory pathways in sickle cell disease: molecular, cellular and translational insights.Frontiers in immunology · 2026Article
- Increased Prevalence of Thromboembolic Events in Patients with Congenital Dyserythropoietic Anemia Type I.Acta haematologica · 2026Article
- Role of hydrogen sulfide in catalyzing the formation of NO-ferroheme.Nitric oxide : biology and chemistry · 2025Article
- An update on extracellular vesicles in hematologic disorders: molecular mediators, clinical biomarkers, and emerging therapeutics.Molecular biology reports · 2025Review
- Innovations in Drug Discovery for Sickle Cell Disease Targeting Oxidative Stress and NRF2 Activation-A Short Review.International journal of molecular sciences · 2025Review
- Hemoglobin S Promotes Glycemic Dysregulation in a Mouse Model of Human Sickle Cell Disease.Endocrinology · 2025Article
93 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intravascular hemolysis describes the relocalization of heme and hemoglobin (Hb) from erythrocytes to plasma. We investigated the concept that erythrocyte membrane microparticles (MPs) concentrate cell-free heme in human hemolytic diseases, and that heme-laden MPs have a physiopathological impact. Up to one-third of cell-free heme in plasma from 47 patients with sickle cell disease (SCD) was sequestered in circulating MPs. Erythrocyte vesiculation in vitro produced MPs loaded with heme. In silico analysis predicted that externalized phosphatidylserine (PS) in MPs may associate with and help retain heme at the cell surface. Immunohistology identified Hb-laden MPs adherent to capillary endothelium in kidney biopsies from hyperalbuminuric SCD patients. In addition, heme-laden erythrocyte MPs adhered and transferred heme to cultured endothelial cells, inducing oxidative stress and apoptosis. In transgenic SAD mice, infusion of heme-laden MPs triggered rapid vasoocclusions in kidneys and compromised microvascular dilation ex vivo. These vascular effects were largely blocked by heme-scavenging hemopexin and by the PS antagonist annexin-a5, in vitro and in vivo. Adversely remodeled MPs carrying heme may thus be a source of oxidant stress for the endothelium, linking hemolysis to vascular injury. This pathway might provide new targets for the therapeutic preservation of vascular function in SCD.
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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.