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Cigarette Smoke–induced Oxidative/Nitrosative Stress Impairs VEGF- and Fluid Shear Stress–Mediated Signaling in Endothelial Cells
- Source :
- Antioxidants & Redox Signaling. 12:1355-1369
- Publication Year :
- 2010
- Publisher :
- Mary Ann Liebert Inc, 2010.
-
Abstract
- VEGF receptor 2 (VEGFR2), a tyrosine kinase receptor, is activated by VEGF and fluid shear stress (FSS), and its downstream signaling is important in the regulation of endothelial functions, such as cell migration, endothelium-dependent relaxation, and angiogenesis. Cigarette smoke (CS) is known to cause oxidative/nitrosative stress, leading to modifications of tyrosine kinase receptors and impaired downstream signaling. We hypothesized that CS-induced oxidative/nitrosative stress impairs VEGF- and FSS-mediated VEGFR2 activation, leading to endothelial dysfunction. Human lung microvascular endothelial cells and human umbilical vein endothelial cells were treated with different concentrations of cigarette smoke extract (CSE) to investigate the VEGF- or FSS-mediated VEGFR2 phosphorylation and its downstream signaling involved in endothelial function. CSE treatment impaired both VEGF- and FSS-mediated VEGFR2 phosphorylation, resulting in impaired endothelial nitric oxide synthase (eNOS) phosphorylation by Akt. CS-derived reactive oxygen/nitrogen species react with VEGFR2, rendering VEGFR2 inactive for its downstream signaling. Pretreatment with nitric oxide scavenger (PTIO), reactive oxygen species scavengers (combination of SOD with catalase), and N-acetyl-l-cysteine, significantly attenuated the CSE-induced impairment of VEGF-mediated Akt and eNOS phosphorylation. These findings suggest that CSE-induced oxidative/nitrosative stress impairs VEGF- and FSS-mediated endothelial cell function and has important implications in the pathogenesis of CS-induced pulmonary and cardiovascular diseases associated with endothelial dysfunction. Antioxid. Redox Signal. 12, 1355–1369.
- Subjects :
- Vascular Endothelial Growth Factor A
Umbilical Veins
Physiology
Angiogenesis
Clinical Biochemistry
Biology
Biochemistry
Cyclic N-Oxides
chemistry.chemical_compound
Smoke
Tobacco
medicine
Humans
Phosphorylation
Endothelial dysfunction
Lung
Molecular Biology
Protein kinase B
Cells, Cultured
Reactive nitrogen species
General Environmental Science
Superoxide Dismutase
Imidazoles
Endothelial Cells
Kinase insert domain receptor
Free Radical Scavengers
Cell Biology
Catalase
medicine.disease
Reactive Nitrogen Species
Vascular Endothelial Growth Factor Receptor-2
humanities
Acetylcysteine
Retraction
Cell biology
Endothelial stem cell
Original Research Communications
Vascular endothelial growth factor A
chemistry
General Earth and Planetary Sciences
Stress, Mechanical
Reactive Oxygen Species
Rheology
Oxidation-Reduction
Protein Processing, Post-Translational
Proto-Oncogene Proteins c-akt
Signal Transduction
Subjects
Details
- ISSN :
- 15577716 and 15230864
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Antioxidants & Redox Signaling
- Accession number :
- edsair.doi.dedup.....31f2370be0f004b4b49e9ce197283a7c