ArticleProceedings of the National Academy of Sciences of the United States of America2016
Gene control of tyrosine kinase TIE2 and vascular manifestations of infections.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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The trial behind it
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Who cites it
67 citing papers in PubMed, 101 citations in OpenAlex.
- Tie2 protects the vasculature against thrombus formation in systemic inflammation.The Journal of clinical investigation · 2018Trial
- Dysregulation of angiopoietin-1 plays a mechanistic role in the pathogenesis of cerebral malaria.Science translational medicine · 2016Trial
- Inactive β1-integrin acts as a junctional scaffold for angiopoietin/TIE2/FOXO1 signaling.The Journal of clinical investigation · 2026Article
- Review
- Endotheliopathy within the thromboinflammatory network of sepsis-induced coagulopathy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Spatial localization of avian and human influenza A virus receptors in male and female bovine reproductive tissues.Scientific reports · 2026Article
- Renal microthrombosis and thrombomodulin deficiency in COVID-19-associated acute kidney injury.BMC nephrology · 2026Observational
- Deletion of the angiopoietin receptor Tie2 enhances proliferation and sprouting of cardiac endothelial cells.Angiogenesis · 2026Article
- CaMKKβ regulates transcription factor Elf2 gene methylation to maintain endothelial junctional barrier integrity.iScience · 2026Article
- Risk stratification of childhood infection using host markers of immune and endothelial activation in Asia (Spot Sepsis): a multi-country, prospective, cohort study.The Lancet. Child & adolescent health · 2025Observational
- Razuprotafib Does Not Improve Microcirculatory Perfusion Disturbances nor Renal Edema in Rats on Extracorporeal Circulation.International journal of molecular sciences · 2025Article
- Expanding RNAi to Kidneys, Lungs, and Spleen via Selective ORgan Targeting (SORT) siRNA Lipid Nanoparticles.Advanced materials (Deerfield Beach, Fla.) · 2024Article
- Intrinsic endothelial hyperresponsiveness to inflammatory mediators drives acute episodes in models of Clarkson disease.The Journal of clinical investigation · 2024Article
- Capillary leak and endothelial permeability in critically ill patients: a current overview.Intensive care medicine experimental · 2023Review
- Cationic LNP-formulated mRNA expressing Tie2-agonist in the lung endothelium prevents pulmonary vascular leakage.Molecular therapy. Nucleic acids · 2023Article
- A ligand-independent Tie2-activating antibody reduces vascular leakage in models of Clarkson disease.Science advances · 2023Article
- Characterization of the Ang/Tie2 Signaling Pathway in the Diaphragm Muscle of DMD Mice.Biomedicines · 2023Article
- The angiopoietin receptor Tie2 is atheroprotective in arterial endothelium.Nature cardiovascular research · 2023Article
- Article
- New Insights into Clinical and Mechanistic Heterogeneity of the Acute Respiratory Distress Syndrome: Summary of the Aspen Lung Conference 2021.American journal of respiratory cell and molecular biology · 2022Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 3 countries.
Funding
Abstract
Ligands of the endothelial-enriched tunica interna endothelial cell kinase 2 (Tie2) are markedly imbalanced in severe infections associated with vascular leakage, yet regulation of the receptor itself has been understudied in this context. Here, we show that TIE2 gene expression may constitute a novel vascular barrier control mechanism in diverse infections. Tie2 expression declined rapidly in wide-ranging models of leak-associated infections, including anthrax, influenza, malaria, and sepsis. Forced Tie2 suppression sufficed to attenuate barrier function and sensitize endothelium to permeability mediators. Rapid reduction of pulmonary Tie2 in otherwise healthy animals attenuated downstream kinase signaling to the barrier effector vascular endothelial (VE)-cadherin and induced vascular leakage. Compared with wild-type littermates, mice possessing one allele of Tie2 suffered more severe vascular leakage and higher mortality in two different sepsis models. Common genetic variants that influence TIE2 expression were then sought in the HapMap3 cohort. Remarkably, each of the three strongest predicted cis-acting SNPs in HapMap3 was also associated with the risk of acute respiratory distress syndrome (ARDS) in an intensive care unit cohort of 1,614 subjects. The haplotype associated with the highest TIE2 expression conferred a 28% reduction in the risk of ARDS independent of other major clinical variables, including disease severity. In contrast, the most common haplotype was associated with both the lowest TIE2 expression and 31% higher ARDS risk. Together, the results implicate common genetic variation at the TIE2 locus as a determinant of vascular leak-related clinical outcomes from common infections, suggesting new tools to identify individuals at unusual risk for deleterious complications of infection.
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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.