The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Cell-based Angiopoietin-1 Gene Therapy for Acute Lung Injury
Abstract
Rationale: The acute respiratory distress syndrome is a significant cause of morbidity and mortality in critically ill patients. Angiopoietin-1 (Ang-1), a ligand for the endothelial Tie2 receptor, is an endothelial survival and vascular stabilization factor that reduces endothelial permeability and inhibits leukocyte–endothelium interactions. Objectives: We hypothesized that Ang-1 counteracts vascular inflammation and pulmonary vascular leak in experimental acute lung injury. Methods: We used cell-based gene therapy in a rat model of ALI. Transgenic mice overexpressing Ang-1 or deficient in the Tie2 receptor were also studied to better elucidate the mechanisms of protection. Measurements and Main Results: The present report provides data that support a strong protective role for the Ang-1/Tie2 system in two experimental models of LPS-induced acute lung injury. In a rat model, cell-based Ang-1 gene transfer improved morphological, biochemical, and molecular indices of lung injury and inflammation. These findings were confirmed in a gain-of-function conditional, targeted transgenic mouse model, in which Ang-1 reduced endothelial cell activation and the expression of adhesion molecules, associated with a marked improvement in airspace inflammation and intraalveolar septal thickening. Moreover, heterozygous Tie2-deficient mice demonstrated enhanced evidence of lung injury and increased early mortality. Conclusions: These results support a critical role for the Ang-1/Tie2 axis in modulating the pulmonary vascular response to lung injury and suggest that Ang-1 therapy may represent a potential new strategy for the treatment and/or prevention of acute respiratory distress syndrome in critically ill patients.
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“Such upregulation may have important clinical implications since VEGF and Ang-1 have been shown to play pivotal roles in angiogenesis, alveolar development, and treatment of acute lung injury (ALI) [8, 57–60].”
From Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells (2018) · cites this paper as [60]
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Metadata
- Authors
- McCarter, S. D., Mei, S. H. J., Lai, P. F. H., Zhang, Q. W., Parker, C. H., Suen, R. S., Hood, R. D., Zhao, Y. D., Deng, Y., Han, R. N. N., Dumont, D. J., & Stewart, D. J.
- Affiliations
- St. Michael's Hospital (CA)
- Sunnybrook Research Institute (CA)
- ORCID
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-05
- Volume
- 175
- Issue
- 10
- Pages
- 1014-1026
- ISSN
- 1073-449X (ISSN-L)
- 1535-4970
- OpenAlex
- W2038968218
- Cited by
- 154
- References
- 54
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 6 · 2021: 9 · 2020: 8 · 2019: 4 · 2018: 11 · 2017: 4 · 2016: 9 · 2015: 9 · 2014: 4 · 2013: 11 · 2012: 11
- FWCI
- 12.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Respiratory and Critical Care Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- angiopoietin-1, Tie2 receptor, acute lung injury, acute respiratory distress syndrome, cell-based gene therapy, endothelial inflammation, leukocyte-endothelial adhesion, lipopolysaccharide-induced lung injury, endothelial activation, adhesion molecules, transgenic mouse model
- MeSH terms
- Animals, Cell Adhesion, Female, Fibroblasts, Lipopolysaccharides, Male, Mice, Transgenic, Rats, Inbred F344, Respiratory Distress Syndrome, Genetic Therapy, Cell Adhesion Molecules, Gene Expression, Cytokines, Angiopoietin-1, Receptor, TIE-2, Mice, Rats
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