ArticleAngiogenesis2021
Depletion of Arg/Abl2 improves endothelial cell adhesion and prevents vascular leak during inflammation.
Article in Angiogenesis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Efficacy and safety of imatinib in patients with COVID-19: a systematic review and meta-analysis.Wiener klinische Wochenschrift · 2025Pooled it
- Efficacy and safety of intravenous imatinib in COVID-19 ARDS: a randomized, double-blind, placebo-controlled clinical trial.Critical care (London, England) · 2023Trial
- Deciphering immune and cellular reprogramming during the progression from inflammatory bowel disease to colorectal cancer using multi-omics single-cell and spatial transcriptomics.Journal of translational medicine · 2026Article
- Measuring and managing pulmonary edema in ARDS: a narrative review.Critical care (London, England) · 2026Review
- Shared molecular mechanisms of vascular endothelial cells in psoriasis and diabetes comorbidity.Postepy dermatologii i alergologii · 2026Article
- Hantaan virus activates Src family kinase and induces endothelial cell hyperpermeability via the TLR4/TRAF6 pathway.Journal of medical microbiology · 2025Article
- Characterization of the Temporal Dynamics of the Endothelial-Mesenchymal-like Transition Induced by Soluble Factors from Dengue Virus Infection in Microvascular Endothelial Cells.International journal of molecular sciences · 2025Article
- Vascular leak in sepsis: physiological basis and potential therapeutic advances.Critical care (London, England) · 2024Review
- Protective effect of isoliquiritigenin in amiodarone-induced damage of human umbilical vein endothelial cells.Immunity, inflammation and disease · 2023Article
- Case Series of Precision Delivery of Methylprednisolone in Pediatric Inflammatory Bowel Disease: Feasibility, Clinical Outcomes, and Identification of a Vasculitic Transcriptional Program.Journal of clinical medicine · 2023Article
- Integrin-Dependent Cell-Matrix Adhesion in Endothelial Health and Disease.Circulation research · 2023Review
- Imatinib attenuates reperfusion injury in a rat model of acute myocardial infarction.Basic research in cardiology · 2023Article
- Endothelial dysfunction triggers acute respiratory distress syndrome in patients with sepsis: a narrative review.Frontiers in medicine · 2023Review
- Article
- Article
- COVID-19 is a systemic vascular hemopathy: insight for mechanistic and clinical aspects.Angiogenesis · 2021Review
- Protectin conjugates in tissue regeneration 1 restores lipopolysaccharide-induced pulmonary endothelial glycocalyx loss via ALX/SIRT1/NF-kappa B axis.Respiratory research · 2021Article
- Sirt3 Maintains Microvascular Endothelial Adherens Junction Integrity to Alleviate Sepsis-Induced Lung Inflammation by Modulating the Interaction of VE-Cadherin andOxidative medicine and cellular longevity · 2021Article
- Study on the Mechanism of Capillary Leakage Caused by Hypoxia-Inducible Factor-1Journal of oncology · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endothelial barrier disruption and vascular leak importantly contribute to organ dysfunction and mortality during inflammatory conditions like sepsis and acute respiratory distress syndrome. We identified the kinase Arg/Abl2 as a mediator of endothelial barrier disruption, but the role of Arg in endothelial monolayer regulation and its relevance in vivo remain poorly understood. Here we show that depletion of Arg in endothelial cells results in the activation of both RhoA and Rac1, increased cell spreading and elongation, redistribution of integrin-dependent cell-matrix adhesions to the cell periphery, and improved adhesion to the extracellular matrix. We further show that Arg is activated in the endothelium during inflammation, both in murine lungs exposed to barrier-disruptive agents, and in pulmonary microvessels of septic patients. Importantly, Arg-depleted endothelial cells were less sensitive to barrier-disruptive agents. Despite the formation of F-actin stress fibers and myosin light chain phosphorylation, Arg depletion diminished adherens junction disruption and intercellular gap formation, by reducing the disassembly of cell-matrix adhesions and cell retraction. In vivo, genetic deletion of Arg diminished vascular leak in the skin and lungs, in the presence of a normal immune response. Together, our data indicate that Arg is a central and non-redundant regulator of endothelial barrier integrity, which contributes to cell retraction and gap formation by increasing the dynamics of adherens junctions and cell-matrix adhesions in a Rho GTPase-dependent fashion. Therapeutic inhibition of Arg may provide a suitable strategy for the treatment of a variety of clinical conditions characterized by vascular leak.
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