Back to Search
Start Over
Effects of nintedanib on the microvascular architecture in a lung fibrosis model
- Source :
- Angiogenesis
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- Nintedanib, a tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis, has anti-fibrotic, anti-inflammatory, and anti-angiogenic activity. We explored the impact of nintedanib on microvascular architecture in a pulmonary fibrosis model. Lung fibrosis was induced in C57Bl/6 mice by intratracheal bleomycin (0.5 mg/kg). Nintedanib was started after the onset of lung pathology (50 mg/kg twice daily, orally). Micro-computed tomography was performed via volumetric assessment. Static lung compliance and forced vital capacity were determined by invasive measurements. Mice were subjected to bronchoalveolar lavage and histologic analyses, or perfused with a casting resin. Microvascular corrosion casts were imaged by scanning electron microscopy and synchrotron radiation tomographic microscopy, and quantified morphometrically. Bleomycin administration resulted in a significant increase in higher-density areas in the lungs detected by micro-computed tomography, which was significantly attenuated by nintedanib. Nintedanib significantly reduced lung fibrosis and vascular proliferation, normalized the distorted microvascular architecture, and was associated with a trend toward improvement in lung function and inflammation. Nintedanib resulted in a prominent improvement in pulmonary microvascular architecture, which outperformed the effect of nintedanib on lung function and inflammation. These findings uncover a potential new mode of action of nintedanib that may contribute to its efficacy in idiopathic pulmonary fibrosis.
- Subjects :
- 0301 basic medicine
Cancer Research
Vital capacity
Pathology
medicine.medical_specialty
Indoles
Physiology
medicine.drug_class
Clinical Biochemistry
Neovascularization, Physiologic
Bleomycin
Article
Tyrosine-kinase inhibitor
03 medical and health sciences
chemistry.chemical_compound
Idiopathic pulmonary fibrosis
Imaging, Three-Dimensional
0302 clinical medicine
Pulmonary fibrosis
medicine
Animals
Intussusceptive angiogenesis
Cell Proliferation
medicine.diagnostic_test
business.industry
Pneumonia
X-Ray Microtomography
respiratory system
medicine.disease
Idiopathic Pulmonary Fibrosis
Respiratory Function Tests
Mice, Inbred C57BL
Pulmonary Alveoli
Disease Models, Animal
030104 developmental biology
Bronchoalveolar lavage
chemistry
030220 oncology & carcinogenesis
Microvessels
Nintedanib
Collagen
business
Subjects
Details
- ISSN :
- 15737209 and 09696970
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Angiogenesis
- Accession number :
- edsair.doi.dedup.....3817ba0baa8f18d14877696571e0edca