ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015
Differential and opposing effects of imatinib on LPS- and ventilator-induced lung injury.
Article in American journal of physiology. Lung cellular and molecular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04794088 (A Randomised, Double-blind, Placebo-controlled Study to Investigate the Safety and Efficacy of Intravenous Imatinib Mesylate), which is not on this map. Cited by 43 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomised, Double-blind, Placebo-controlled Study to Investigate the Safety and Efficacy of Intravenous Imatinib Mesylate (Impentri®) in Subjects With Acute Respiratory Distress Syndrome Induced by COVID-19
Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 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
- Immunomodulation and endothelial barrier protection mediate the association between oral imatinib and mortality in hospitalised COVID-19 patients.The European respiratory journal · 2022Trial
- IFN-γ drives inflammatory bowel disease pathogenesis through VE-cadherin-directed vascular barrier disruption.The Journal of clinical investigation · 2019Trial
- Hyaluronic Acid-Decorated Liposomes for the Intrapulmonary Delivery of Imatinib: A Targeted Treatment for Postinflammatory Pulmonary Fibrosis.Small science · 2025Article
- Experimental animal models of acute respiratory distress syndrome: one-hit and two-hit establishment application.Frontiers in immunology · 2025Review
- Cellular Mechanisms of Lung Injury: Current Perspectives.Clinics in chest medicine · 2024Review
- Endothelium as a Source of Cardiovascular Toxicity From Antitumor Kinase Inhibitors.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Assessment of Imatinib Anti-Remodeling Activity on a Human Precision Cut Lung Slices Model.International journal of molecular sciences · 2024Article
- Longitudinal plasma proteomics reveals biomarkers of alveolar-capillary barrier disruption in critically ill COVID-19 patients.Nature communications · 2024Article
- The impact of intravenous dodecafluoropentane on a murine model of acute lung injury.Intensive care medicine experimental · 2023Article
- Article
- Intravenous Injection of Na Ions Aggravates Ang II-Induced Hypertension-Related Vascular Endothelial Injury by Increasing Transmembrane Osmotic Pressure.International journal of nanomedicine · 2023Article
- Endothelial dysfunction triggers acute respiratory distress syndrome in patients with sepsis: a narrative review.Frontiers in medicine · 2023Review
- A cortactin CTTN coding SNP contributes to lung vascular permeability and inflammatory disease severity in African descent subjects.Translational research : the journal of laboratory and clinical medicine · 2022Article
- Imatinib alleviates lung injury and prolongs survival in ventilated rats.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Critical role for the lung endothelial nonmuscle myosin light-chain kinase isoform in the severity of inflammatory murine lung injury.Pulmonary circulation · 2022Article
- c-Abl kinase regulates neutrophil extracellular trap formation and lung injury in abdominal sepsis.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Article
- MRSA-induced endothelial permeability and acute lung injury are attenuated by FTY720 S-phosphonate.American journal of physiology. Lung cellular and molecular physiology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Endothelial dysfunction underlies the pathophysiology of vascular disorders such as acute lung injury (ALI) syndromes. Recent work has identified the Abl family kinases (c-Abl and Arg) as important regulators of endothelial cell (EC) barrier function and suggests that their inhibition by currently available pharmaceutical agents such as imatinib may be EC protective. Here we describe novel and differential effects of imatinib in regulating lung pathophysiology in two clinically relevant experimental models of ALI. Imatinib attenuates endotoxin (LPS)-induced vascular leak and lung inflammation in mice but exacerbates these features in a mouse model of ventilator-induced lung injury (VILI). We next explored these discrepant observations in vitro through investigation of the roles for Abl kinases in cultured lung EC. Imatinib attenuates LPS-induced lung EC permeability, restores VE-cadherin junctions, and reduces inflammation by suppressing VCAM-1 expression and inflammatory cytokine (IL-8 and IL-6) secretion. Conversely, in EC exposed to pathological 18% cyclic stretch (CS) (in vitro model of VILI), imatinib decreases VE-cadherin expression, disrupts cell-cell junctions, and increases IL-8 levels. Downregulation of c-Abl expression with siRNA attenuates LPS-induced VCAM-1 expression, whereas specific reduction of Arg reduces VE-cadherin expression in 18% CS-challenged ECs to mimic the imatinib effects. In summary, imatinib exhibits pulmonary barrier-protective and anti-inflammatory effects in LPS-injured mice and lung EC; however, imatinib exacerbates VILI as well as dysfunction in 18% CS-EC. These findings identify the Abl family kinases as important modulators of EC function and potential therapeutic targets in lung injury syndromes.
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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.