Angiogenic growth factors in the pathophysiology of a murine model of acute lung injury.
Capillary leakage and alveolar edema are hallmarks of acute lung injury (ALI). Neutrophils and serum macromolecules enter alveoli, promoting inflammation. Vascular endothelial growth factor (VEGF) causes plasma leakage in extrapulmonary vessels. Angiopoietin (Ang)-1 and -4 stabilize vessels, attenuating capillary leakage. We hypothesized that VEGF and Ang-1 and -4 modulate vessel leakage in the lung, contributing to the pathogenesis of ALI. We examined a murine model of lipopolysaccharide (LPS)-induced ALI. C57BL/6 and 129/J mice were studied at baseline and 24, 48, and 96 h after single or multiple doses of aerosolized LPS. Both strains exhibited time- and dose-dependent increases in inflammation and a deterioration of lung mechanics. Bronchoalveolar lavage (BAL) protein levels increased significantly, suggesting capillary leakage. Increased BAL neutrophil and total protein content correlated with time-dependent increased tissue VEGF and decreased Ang-1 and -4 levels, with peak VEGF and minimum Ang-1 and -4 expression after 96 h of LPS challenge. These data suggest that changes in the balance between VEGF and Ang-1 and -4 after LPS exposure may modulate neutrophil influx, protein leakage, and alveolar flooding during early ALI.
Duke Scholars
Altmetric Attention Stats
Dimensions Citation Stats
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Vascular Endothelial Growth Factors
- Vascular Endothelial Growth Factor A
- Respiratory System
- Nebulizers and Vaporizers
- Mice, Inbred Strains
- Mice, Inbred C57BL
- Mice
- Membrane Glycoproteins
- Lymphokines
- Lung Diseases
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Vascular Endothelial Growth Factors
- Vascular Endothelial Growth Factor A
- Respiratory System
- Nebulizers and Vaporizers
- Mice, Inbred Strains
- Mice, Inbred C57BL
- Mice
- Membrane Glycoproteins
- Lymphokines
- Lung Diseases