ArticleAmerican journal of respiratory and critical care medicine2012
Absence of integrin αvβ3 enhances vascular leak in mice by inhibiting endothelial cortical actin formation.
Article in American journal of respiratory and critical care medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 92 citations in OpenAlex.
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- Endothelial αvβ3 integrin induction during hypoxia protects blood-brain barrier integrity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Therapeutic potential of integrins in diabetic retinopathy.World journal of diabetes · 2025Review
- The potential role of the αVβ3 integrin receptor in placental biology and normal and complicated pregnancies.British journal of haematology · 2025Review
- Pharmacological blocking of microfibrillar-associated protein 4 reduces retinal neoangiogenesis and vascular leakage.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Early identification and diagnosis, pathophysiology, and treatment of sepsis-related acute lung injury: a narrative review.Journal of thoracic disease · 2024Review
- CC5 and CC8, Two Disintegrin Isoforms fromInternational journal of molecular sciences · 2023Article
- Integrin-Dependent Cell-Matrix Adhesion in Endothelial Health and Disease.Circulation research · 2023Review
- Modulation of low-dose ozone and LPS exposed acute mouse lung inflammation by IF1 mediated ATP hydrolysis inhibitor, BTB06584.Frontiers in immunology · 2023Article
- Deep Learning Chest CT for Clinically Precise Prediction of Sepsis-Induced Acute Respiratory Distress Syndrome: A Protocol for an Observational Ambispective Cohort Study.Healthcare (Basel, Switzerland) · 2022Article
- Traffic Patterns of the Migrating Endothelium: How Force Transmission Regulates Vascular Malformation and Functional Shunting During Angiogenic Remodelling.Frontiers in cell and developmental biology · 2022Article
- Designing Cardiovascular Implants Taking in View the Endothelial Basement Membrane.International journal of molecular sciences · 2021Review
- Integrin αvβ8 on T cells suppresses anti-tumor immunity in multiple models and is a promising target for tumor immunotherapy.Cell reports · 2021Article
- Non-oncological applications of RGD-based single-photon emission tomography and positron emission tomography agents.European journal of nuclear medicine and molecular imaging · 2021Review
- Article
- CC17 group B Streptococcus exploits integrins for neonatal meningitis development.The Journal of clinical investigation · 2021Article
- The β3/5 Integrin-MMP9 Axis Regulates Pulmonary Inflammatory Response and Endothelial Leakage in Acute Lung Injury.Journal of inflammation research · 2021Article
- SARS-CoV-2 uses major endothelial integrin αvβ3 to cause vascular dysregulation in-vitro during COVID-19.PloS one · 2021Article
- Tea Polyphenols Prevent Sepsis-Induced Lung Injury via Promoting Translocation of DJ-1 to Mitochondria.Frontiers in cell and developmental biology · 2021Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
rationaleSepsis and acute lung injury (ALI) have devastatingly high mortality rates. Both are associated with increased vascular leak, a process regulated by complex molecular mechanisms.
objectivesWe hypothesized that integrin αvβ3 could be an important determinant of vascular leak and endothelial permeability in sepsis and ALI.
methodsβ3 subunit knockout mice were tested for lung vascular leak after endotracheal LPS, and systemic vascular leak and mortality after intraperitoneal LPS and cecal ligation and puncture. Possible contributory effects of β3 deficiency in platelets and other hematopoietic cells were excluded by bone marrow reconstitution experiments. Endothelial cells treated with αvβ3 antibodies were evaluated for sphingosine-1 phosphate (S1P)–mediated alterations in barrier function, cytoskeletal arrangement, and integrin localization. MEASUREMENTS AND MAIN
resultsβ3 knockout mice had increased vascular leak and pulmonary edema formation after endotracheal LPS, and increased vascular leak and mortality after intraperitoneal LPS and cecal ligation and puncture. In endothelial cells, αvβ3 antibodies inhibited barrier-enhancing and cortical actin responses to S1P. Furthermore, S1P induced translocation of αvβ3 from discrete focal adhesions to cortically distributed sites through Gi- and Rac1-mediated pathways. Cortical αvβ3 localization after S1P was decreased by αvβ3 antibodies, suggesting that ligation of the αvβ3 with its extracellular matrix ligands is required to stabilize cortical αvβ3 focal adhesions.
conclusionsOur studies identify a novel mechanism by which αvβ3 mitigates increased vascular leak, a pathophysiologic function central to sepsis and ALI. These studies suggest that drugs designed to block αvβ3 may have the unexpected side effect of intensifying sepsis- and ALI-associated vascular endothelial leak.
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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.