ArticleCritical care (London, England)2011
The synthetic tie2 agonist peptide vasculotide protects against vascular leakage and reduces mortality in murine abdominal sepsis.
Article in Critical care (London, England), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.
- Exploring the Impact of Extracorporeal Membrane Oxygenation on the Endothelium: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Clinical and biochemical endpoints and predictors of response to plasma exchange in septic shock: results from a randomized controlled trial.Critical care (London, England) · 2022Trial
- Neutrophil extracellular traps-associated candidate genes in IgA vasculitis: an exploratory multi-omics analysis integrating transcriptomics and Mendelian randomization.Pediatric rheumatology online journal · 2026Article
- Pre-Exposure Prophylaxis with Vasculotide Enhances Survival and Alleviates Hematopoietic and Gastrointestinal Injury Following Lethal Total Body Irradiation.International journal of molecular sciences · 2026Article
- Endotheliopathy in CAR T-Cell Therapy: Mechanistic Insights into the VWF/ADAMTS13 Axis and the Angiopoietin-Tie2 Pathway.TH open : companion journal to thrombosis and haemostasis · 2026Review
- Tie2-Dependent Mechanisms Influence Leptomeningeal Collateral Dynamics and Reperfusion Following Stroke.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Septic shock in the era of precision medicine: rethinking fluids, vasopressors, and immunomodulation.Frontiers in medicine · 2026Review
- Angiopoietin-2 adsorption attempt with the cytokine adsorber cytosorb in critically ill patients.Scientific reports · 2025Article
- Dialysis and cognitive impairment.Nature reviews. Nephrology · 2025Review
- Vascular leakage during circulatory failure: physiopathology, impact and treatments.Annals of intensive care · 2025Review
- Razuprotafib Does Not Improve Microcirculatory Perfusion Disturbances nor Renal Edema in Rats on Extracorporeal Circulation.International journal of molecular sciences · 2025Article
- Unfractionated heparin attenuated histone-induced pulmonary endothelial glycocalyx injury through Ang/Tie2 pathway.Journal of inflammation (London, England) · 2025Article
- Molecular mechanisms and therapeutic advances of peritubular capillary neogenesis in acute kidney injury.Frontiers in molecular biosciences · 2025Review
- Cellular Mechanisms of Lung Injury: Current Perspectives.Clinics in chest medicine · 2024Review
- Vascular leak in sepsis: physiological basis and potential therapeutic advances.Critical care (London, England) · 2024Review
- Endothelial and inflammatory pathophysiology in dengue shock: New insights from a prospective cohort study in Vietnam.PLoS neglected tropical diseases · 2024Observational
- Review
- A ligand-independent Tie2-activating antibody reduces vascular leakage in models of Clarkson disease.Science advances · 2023Article
- Endothelial deletion of EPH receptor A4 alters single-cell profile and Tie2/Akap12 signaling to preserve blood-brain barrier integrity.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
introductionAngiopoietin-1 (Angpt1), the natural agonist ligand for the endothelial Tie2 receptor, is a non-redundant endothelial survival and vascular stabilization factor that reduces endothelial permeability and inhibits leukocyte-endothelium interactions. Here we evaluate the efficacy of a novel polyethylene glycol (PEG)-clustered Tie2 agonist peptide, Vasculotide (VT), to protect against vascular leakage and mortality in a murine model of polymicrobial abdominal sepsis.
methodsPolymicrobial abdominal sepsis in C57BL6 mice was induced by cecal-ligation-and-puncture (CLP). Mice were treated with different dosages of VT or equal volume of phosphate-buffered saline (PBS). Sham-operated animals served as time-matched controls.
resultsSystemic administration of VT induced long-lasting Tie2 activation in vivo. VT protected against sepsis-induced endothelial barrier dysfunction, as evidenced by attenuation of vascular leakage and leukocyte transmigration into the peritoneal cavity. Histological analysis revealed that VT treatment ameliorated leukocyte infiltration in kidneys of septic mice, probably due to reduced endothelial adhesion molecule expression. VT-driven effects were associated with significantly improved organ function and reduced circulating cytokine levels. The endothelial-specific action of VT was supported by additional in vitro studies showing no effect of VT on either cytokine release from isolated peritoneal macrophages, or migratory capacity of isolated neutrophils. Finally, administration of VT pre-CLP (Hazard Ratio 0.39 [95% Confidence interval 0.19-0.81] P < 0.001) and post-CLP reduced mortality in septic mice (HR 0.22 [95% CI 0.06-0.83] P < 0.05).
conclusionsWe provide proof of principle in support of the efficacious use of PEGylated VT, a drug-like Tie2 receptor agonist, to counteract microvascular endothelial barrier dysfunction and reduce mortality in a clinically relevant murine sepsis model. Further studies are needed to pave the road for clinical application of this therapeutic concept.
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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.