ArticleBlood2015
Hydroxyurea with AKT2 inhibition decreases vaso-occlusive events in sickle cell disease mice.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Whole Blood Transcriptomic Analysis of Sickle Cell Trait.European journal of haematology · 2026Article
- Beneficial effects of SGLT1/2 and SGLT2 inhibitors on vaso-occlusive events and organ damage in sickle cell disease mice.Cardiovascular research · 2026Article
- Neutrophil DREAM promotes neutrophil recruitment in vascular inflammation.The Journal of experimental medicine · 2022Article
- Impact of Abnormal Leukocyte Count in the Pathophysiology of Sickle Cell Anemia.Journal of blood medicine · 2022Article
- Nitric Oxide Synthase Dependency in Hydroxyurea Inhibition of Erythroid Progenitor Growth.Genes · 2021Article
- Repurposing pyridoxamine for therapeutic intervention of intravascular cell-cell interactions in mouse models of sickle cell disease.Haematologica · 2020Article
- Role of the coagulation system in the pathogenesis of sickle cell disease.Blood advances · 2019Article
- Platelet Protein Disulfide Isomerase Promotes Glycoprotein Ibα-Mediated Platelet-Neutrophil Interactions Under Thromboinflammatory Conditions.Circulation · 2019Article
- Therapeutic strategies for sickle cell disease: towards a multi-agent approach.Nature reviews. Drug discovery · 2019Review
- Ser/Thr protein kinase Bβ-NADPH oxidase 2 signaling in thromboinflammation.Current opinion in hematology · 2017Review
- ARQ 092, an orally-available, selective AKT inhibitor, attenuates neutrophil-platelet interactions in sickle cell disease.Haematologica · 2017Article
- Increased Vasoocclusive Crises in "O" Blood Group Sickle Cell Disease Patients: Association with Underlying Thrombospondin Levels.Mediterranean journal of hematology and infectious diseases · 2017Article
- New insights into sickle cell disease: mechanisms and investigational therapies.Current opinion in hematology · 2016Review
- Neutrophils, platelets, and inflammatory pathways at the nexus of sickle cell disease pathophysiology.Blood · 2016Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Heterotypic cell-cell adhesion and aggregation mediate vaso-occlusive events in patients with sickle cell disease (SCD). Although hydroxyurea (HU), an inducer of fetal hemoglobin, is the main therapy for treatment of SCD, it is unclear whether it has immediate benefits in acute vaso-occlusive events in SCD patients. Using real-time fluorescence intravital microscopy, we demonstrated that short-term coadministration of HU and Akti XII, an AKT2 inhibitor, efficiently reduced neutrophil adhesion and platelet-neutrophil aggregation in venules of Berkeley (SCD) mice challenged with tumor necrosis factor α (TNF-α) or hypoxia/reoxygenation. Importantly, compared with HU or Akti XII treatment alone, short-term treatment with both agents significantly improved survival in those mice. We found that the level of plasma nitric oxide species was elevated by HU but not Akti XII, AKT2 phosphorylation levels in activated neutrophils and platelets were reduced by Akti XII but not HU, and the expression of endothelial E-selectin and intercellular adhesion molecule 1 was decreased by either agent. Our results suggest that short-term coadministration of HU and Akti XII has immediate benefits for acute vaso-occlusive events and survival in SCD mice exceeding those seen for single therapy.
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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.