ArticleThe American journal of pathology2011
Neutrophil elastase is produced by pulmonary artery smooth muscle cells and is linked to neointimal lesions.
Article in The American journal of pathology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 93 citations in OpenAlex.
- Tiprelestat for treatment of hospitalized COVID-19: results of the double-blind randomized placebo-controlled COMCOVID trial.Advances in therapy · 2025Trial
- Elastokines are potentially associated with a poor prognosis in idiopathic pulmonary fibrosis.Scientific reports · 2026Article
- Elastokines are Associated with a Poor Prognosis in Idiopathic Pulmonary Fibrosis.Research square · 2025Article
- Long-term outcomes and prognostic predictors in patients with fibrosing mediastinitis associated pulmonary hypertension: a multicenter cohort study.Orphanet journal of rare diseases · 2025Article
- Therapeutic targets for pulmonary arterial hypertension: insights into the emerging landscape.Expert opinion on therapeutic targets · 2025Review
- Current Overview of the Biology and Pharmacology in Sugen/Hypoxia-Induced Pulmonary Hypertension in Rats.Journal of aerosol medicine and pulmonary drug delivery · 2024Review
- Current Mouse Models of Intracranial Aneurysms: Analysis of Pharmacological Agents Used to Induce Aneurysms and Their Impact on Translational Research.Journal of the American Heart Association · 2024Review
- S100A4 Is a Key Facilitator of Thoracic Aortic Dissection.International journal of biological sciences · 2024Article
- The role of immune cells and inflammation in pulmonary hypertension: mechanisms and implications.Frontiers in immunology · 2024Review
- A computational growth and remodeling framework for adaptive and maladaptive pulmonary arterial hemodynamics.Biomechanics and modeling in mechanobiology · 2023Article
- Pulmonary fibroelastosis - A review.Matrix biology : journal of the International Society for Matrix Biology · 2023Review
- Pentastatin, a matrikine of the collagen IVα5, is a novel endogenous mediator of pulmonary endothelial dysfunction.American journal of physiology. Cell physiology · 2023Article
- PAR2 activation in the dura causes acute behavioral responses and priming to glyceryl trinitrate in a mouse migraine model.The journal of headache and pain · 2023Article
- New Drugs and Therapies in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2023Review
- Pulmonary Vascular Remodeling in Pulmonary Hypertension.Journal of personalized medicine · 2023Review
- Endogenous Retroviral Elements Generate Pathologic Neutrophils in Pulmonary Arterial Hypertension.American journal of respiratory and critical care medicine · 2022Article
- Systemic Inflammation Is Associated with Pulmonary Hypertension in Isolated Giant Omphalocele: A Population-Based Study.Healthcare (Basel, Switzerland) · 2022Article
- Elastin turnover in ocular diseases: A special focus on age-related macular degeneration.Experimental eye research · 2022Review
- Nets, pulmonary arterial hypertension, and thrombo-inflammation.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Construction of a diagnostic signature and immune landscape of pulmonary arterial hypertension.Frontiers in cardiovascular medicine · 2022Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Previously, we reported that murine gammaherpesvirus-68 (M1-MHV-68) induces pulmonary artery (PA) neointimal lesions in S100A4-overexpressing, but not in wild-type (C57), mice. Lesions were associated with heightened lung elastase activity and PA elastin degradation. We now investigate a direct relationship between elastase and PA neointimal lesions, the nature and source of the enzyme, and its presence in clinical disease. We found an association exists between the percentage of PAs with neointimal lesions and elastin fragmentation in S100A4 mice 6 months after viral infection. Confocal microscopy documented the heightened susceptibility of S100A4 versus C57 PA elastin to degradation by elastase. A transient increase in lung elastase activity occurs in S100A4 mice, 7 days after M1-MHV-68, unrelated to inflammation or viral load and before neointimal lesions. Administration of recombinant elafin, an elastase-specific inhibitor, ameliorates early increases in serine elastase and attenuates later development of neointimal lesions. Neutrophils are the source of elevated elastase (NE) in the S100A4 lung, and NE mRNA and protein levels are greater in PA smooth muscle cells (SMC) from S100A4 mice than from C57 mice. Furthermore, elevated NE is observed in cultured PA SMC from idiopathic PA hypertension versus that in control lungs and localizes to neointimal lesions. Thus, PA SMC produce NE, and heightened production and activity of NE is linked to experimental and clinical pulmonary vascular disease.
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