VEGF mediates fat embolism-induced acute lung injury via VEGF receptor 2 and the MAPK cascade

Autor: Yu-Hao Lin, Chin-Kuo Lin, Chung-Sheng Shi, Tai-Chun Huang, Cheng-Ta Yang, Yi Ling Yang
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
Vascular Endothelial Growth Factor A
0301 basic medicine
MAPK/ERK pathway
ARDS
Angiogenesis
Interleukin-1beta
Nitric Oxide Synthase Type II
lcsh:Medicine
Vascular permeability
Rats
Sprague-Dawley
chemistry.chemical_compound
0302 clinical medicine
Phosphorylation
lcsh:Science
Lung
Micelles
Respiratory Distress Syndrome
Multidisciplinary
biology
Respiration
Pulmonary edema
Experimental models of disease
Vascular endothelial growth factor
Nitric oxide synthase
Mitogen-Activated Protein Kinases
Signal Transduction
medicine.medical_specialty
Acute Lung Injury
Embolism
Fat
Pulmonary Edema
Lung injury
Article
03 medical and health sciences
Internal medicine
medicine
Animals
business.industry
lcsh:R
medicine.disease
Vascular Endothelial Growth Factor Receptor-2
Rats
030104 developmental biology
Endocrinology
Gene Expression Regulation
chemistry
biology.protein
lcsh:Q
business
030217 neurology & neurosurgery
Zdroj: Scientific Reports, Vol 9, Iss 1, Pp 1-8 (2019)
Scientific Reports
ISSN: 2045-2322
DOI: 10.1038/s41598-019-47276-4
Popis: Fat embolism (FE) is a lethal medical emergency often caused by fracture of long bones and amputation of limbs. Vascular endothelial growth factor (VEGF) promotes angiogenesis and increases vascular permeability. We tested the hypothesis that VEGF plays a critical role in FE-induced acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). Fat tissues were collected from male Sprague-Dawley rats, and animal oil was extracted and mixed with water to form fatty micelles. The micelles were then injected into the tail vein to produce FE and ALI in rats. Lung weight gain was measured as the index of pulmonary edema. The expression of pulmonary VEGF was evaluated by real-time PCR and western blot analysis. Inducible nitric oxide synthase (iNOS) and phosphorylation of mitogen-activated protein kinase (MAPK) were determined by western blot analyses. Interleukin-1β (IL-1β) was quantified by ELISAs. Hematoxylin and eosin staining was used to evaluate the pathological damage of ALI. In this study, we found that animal oil-induced FE significantly increased pulmonary VEGF expression and MAPK phosphorylation. We also evaluated the inflammatory response after FE and found that iNOS and IL-1β significantly increased after FE. Systemic administration of SU-1498, an antagonist of VEGF receptor 2 (VEGFR-2), significantly attenuated the FE-induced inflammatory response and histological damage. This study suggested that VEGF is involved in FE-induced ARDS via the VEGFR-2 and MAPK cascades, which induce IL-1β release and iNOS upregulation. Blockade of could be used to treat FE-induced pulmonary damage.
Databáze: OpenAIRE
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