ArticleJCI insight2021
Tie2 activation protects against prothrombotic endothelial dysfunction in COVID-19.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Endotheliopathy in Acute COVID-19 and Long COVID.International journal of molecular sciences · 2023Pooled it
- Targeting CD148 for Antithrombotic Therapy: Functional and Molecular Evaluation of AKB-9778.Pharmacology research & perspectives · 2026Article
- Renal microthrombosis and thrombomodulin deficiency in COVID-19-associated acute kidney injury.BMC nephrology · 2026Observational
- Immune-endothelial-coagulation crosstalk as a driver of multi-organ dysfunction in severe viral pneumonia.Frontiers in immunology · 2026Review
- Multiomics reveal plasma constituents associated with thrombosis among trauma patients who do not respond to enoxaparin.Blood vessels, thrombosis & hemostasis · 2025Article
- Role of Tie-2 Axis in Sepsis: A Potential Therapeutic Target.Journal of cellular and molecular medicine · 2025Review
- Thrombomodulin resistance as a novel prothrombotic pathway in COVID-19.Scientific reports · 2025Article
- Inflammatory, fibrotic and endothelial biomarker profiles in COVID-19 patients during and following hospitalization.Scientific reports · 2025Article
- Endothelial cell activation enhances thromboinflammation in vaccine-induced immune thrombotic thrombocytopenia.Blood advances · 2025Article
- Cathepsin K cleavage of angiopoietin-2 creates detrimental Tie2 antagonist fragments in sepsis.The Journal of clinical investigation · 2025Article
- Article
- Possibility of Using NO Modulators for Pharmacocorrection of Endothelial Dysfunction After Prenatal Hypoxia.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Enhanced prediction of thrombotic events in hospitalized COVID-19 patients with soluble thrombomodulin.PloS one · 2025Article
- A cell-based model to study mechanisms of endothelial-dependent thrombin generation in response to inflammation and its modulation by hydroxychloroquine.Research and practice in thrombosis and haemostasis · 2025Article
- Delineating sex-specific circulating host response signatures associated with COVID-19 severity and mortality.iScience · 2024Article
- The Contribution of Neutrophil Extracellular Traps to Coagulopathy in Patients with COVID-19-Related Thrombosis.Viruses · 2024Article
- Esm-1 mediates transcriptional polarization associated with diabetic kidney disease.American journal of physiology. Renal physiology · 2024Article
- A machine learning algorithm for peripheral artery disease prognosis using biomarker data.iScience · 2024Article
- Reduction of renal interstitial fibrosis by targeting Tie2 in vascular endothelial cells.Pediatric research · 2024Article
- Designer high-density lipoprotein particles enhance endothelial barrier function and suppress inflammation.Science signaling · 2024Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
Endothelial dysfunction accompanies the microvascular thrombosis commonly observed in severe COVID-19. Constitutively, the endothelial surface is anticoagulant, a property maintained at least in part via signaling through the Tie2 receptor. During inflammation, the Tie2 antagonist angiopoietin-2 (Angpt-2) is released from endothelial cells and inhibits Tie2, promoting a prothrombotic phenotypic shift. We sought to assess whether severe COVID-19 is associated with procoagulant endothelial dysfunction and alterations in the Tie2/angiopoietin axis. Primary HUVECs treated with plasma from patients with severe COVID-19 upregulated the expression of thromboinflammatory genes, inhibited the expression of antithrombotic genes, and promoted coagulation on the endothelial surface. Pharmacologic activation of Tie2 with the small molecule AKB-9778 reversed the prothrombotic state induced by COVID-19 plasma in primary endothelial cells. Lung autopsies from patients with COVID-19 demonstrated a prothrombotic endothelial signature. Assessment of circulating endothelial markers in a cohort of 98 patients with mild, moderate, or severe COVID-19 revealed endothelial dysfunction indicative of a prothrombotic state. Angpt-2 concentrations rose with increasing disease severity, and the highest levels were associated with worse survival. These data highlight the disruption of Tie2/angiopoietin signaling and procoagulant changes in endothelial cells in severe COVID-19. Our findings provide rationale for current trials of Tie2-activating therapy with AKB-9778 in COVID-19.
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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.