ArticleCells2022
Neutrophil Elastase Increases Vascular Permeability and Leukocyte Transmigration in Cultured Endothelial Cells and Obese Mice.
Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 39 citations in OpenAlex.
- The protease code of the bacterial gut microbiota: ecological regulation, barrier disruption, and rewiring host defense and signaling.Gut microbes · 2026Review
- Immature Neutrophil Phenotype and Enhanced Myeloperoxidase in Male Patients With Chronic Kidney Disease and Cardiovascular Comorbidity.Acta physiologica (Oxford, England) · 2026Article
- MMP8 exacerbates sepsis-induced pulmonary vascular leakage by disruption of endothelial VE-cadherin through ERK signalling.Molecular biomedicine · 2026Article
- Extracellular Vesicles as Drivers of Lung Endothelial Dysfunction in ARDS: Mechanisms and Therapeutic Opportunities.Comprehensive Physiology · 2026Review
- Dysregulated iron metabolism associates with neutrophilic airway inflammation in COPD.Clinical science (London, England : 1979) · 2026Article
- Protease-activated receptors act as a liaison between metabolism and inflammation.Inflammopharmacology · 2026Review
- Bioresorbable Vascular Stents: How Neutrophil Extracellular Traps Influence Biocompatibility, Degradation Kinetics, and Device Performance.Bioengineering (Basel, Switzerland) · 2026Review
- Role of neutrophils in regulating vascular permeability in inflammatory and autoimmune diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Sivelestat sodium mitigates lung injury post-acute pulmonary embolism by inhibiting NE-SPP1 neutrophil recruitment and restoring redox balance.Scientific reports · 2026Article
- Unveiling the immune microenvironment in diabetic nephropathy: from mechanisms to therapeutics.Frontiers in immunology · 2026Review
- Neutrophil extracellular traps contribute significantly to vascular dysfunction in sepsis.Frontiers in pharmacology · 2026Review
- Human M-MDSCs impair neutrophil migration in the infectious microenvironment.Journal of leukocyte biology · 2025Article
- Modeling antithymocyte globulin-induced microvasculopathy using human iPSC-derived vascularized liver organoids.Cell reports. Medicine · 2025Article
- High‑dose X‑ray irradiation induces NETosis via the eCIRP/TREM‑1 axis in mouse neutrophils.International journal of molecular medicine · 2025Article
- Neutrophil-to-lymphocyte and monocyte-to-lymphocyte ratios as inflammatory markers in the assessment of glycemic status in diabetic patients of Asir region.Animal models and experimental medicine · 2025Article
- Pathophysiological Role of Neutrophil Extracellular Traps in Diet-Induced Obesity and Metabolic Syndrome in Animal Models.Nutrients · 2025Review
- The NE/AAT/CBG axis regulates adipose tissue glucocorticoid exposure.Nature communications · 2025Article
- Decoding the Nonlinear Association Between Visceral Adiposity Index and All-Cause Mortality: The Mediating Role of White Blood Cells and Neutrophils.International journal of endocrinology · 2025Article
- Sex-specific effects of peptidyl arginine deiminase 4 deficiency in the cafeteria diet-induced obesity-associated metabolic complications.Frontiers in endocrinology · 2025Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Neutrophil elastase (NE) plays a pivotal role in inflammation. However, the mechanism underlying NE-mediated inflammation in obesity remains unclear. Here, we report that NE activates protease-activated receptor-2 (PAR2), stimulates actin filament (F-actin) formation, decreases intercellular junction molecule VE-cadherin expression, and increases the permeability of human arterial endothelial cells (hECs). NE also prompts degradation of VE-cadherin and its binding proteins p120- and β-catenins via MG132-sensitive proteasomes. NE stimulates phosphorylation of myosin light-chain (MLC) and its regulator myosin phosphatase target subunit-1 (MYPT1), a target of Rho kinase (ROCK). Inhibitors of PAR2 and ROCK prohibit NE-induced F-actin formation, MLC phosphorylation, and VE-cadherin reduction in hECs, and impede monocyte transmigration through hEC monolayer pretreated with either neutrophils or NE. Further, administration of an NE inhibitor GW311616A significantly attenuates vascular leakage, leukocyte infiltration, and the expression of proinflammatory cytokines in the white adipose tissue from high-fat diet (HFD)-induced obese mice. Likewise, NE-deficient mice are resistant to HFD-induced vascular leakage in the heart. Together, NE regulates actomyosin cytoskeleton activity and VE-cadherin expression by activating PAR2 signaling in the endothelial cells, leading to increased vascular permeability and leukocyte extravasation. Hence, inhibition of NE is a potential approach to mitigate vascular injury and leukocyte infiltration in obesity-related systemic inflammation.
Indexed as
Identifiers
What OpenQuestion holds
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.