Angiopoietin-1 and VEGF in vascular development and angiogenesis in hypoplastic lungs
| Autor: | Mala R. Chinoy, Megan M. Graybill, Gordon L. Kauffman, Shane Miller, C. Max Lang |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Vascular Endothelial Growth Factor A
Pulmonary and Respiratory Medicine MAP Kinase Signaling System Physiology Angiogenesis Endothelial Growth Factors Biology Mice chemistry.chemical_compound Vasculogenesis Pregnancy Physiology (medical) Angiopoietin-1 medicine Animals Receptors Growth Factor Pesticides Coloring Agents Lung Hernia Diaphragmatic Mitogen-Activated Protein Kinase 1 Lymphokines Membrane Glycoproteins Mitogen-Activated Protein Kinase 3 Neovascularization Pathologic Vascular Endothelial Growth Factors Phenyl Ethers Embryogenesis Receptor Protein-Tyrosine Kinases Cell Biology respiratory system Nitrofen Immunohistochemistry Carbon Enzyme Activation Vascular endothelial growth factor Receptors Vascular Endothelial Growth Factor medicine.anatomical_structure chemistry Immunology Circulatory system Cancer research Female Mitogen-Activated Protein Kinases Blood vessel |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 283:L60-L66 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.00317.2001 |
| Popis: | We hypothesized that exposure of murine fetuses to environmental toxins, such as nitrofen, during early embryogenesis alters vasculogenesis. To address our hypothesis, we assessed protein levels of endothelial cell-selective angiogenic factors: angiopoietin (ANG)-1, vascular endothelial growth factor (VEGF), and mediator of VEGF signaling, VEGF receptor-2 [fetal liver kinase (Flk)-1], a transmembrane receptor tyrosine kinase. VEGF and Flk-1 proteins were lower in hypoplastic lungs from pseudoglandular to alveolar stages than in normal lungs at equivalent developmental time points significant for induction of pulmonary vasculogenesis and angiogenesis. ANG-1 protein was higher in hypoplastic lungs than in normal lungs at all the developmental stages considered in this study, i.e., pseudoglandular, canalicular, saccular, and alveolar stages. We assessed exogenous VEGF-mediated endothelial cell response on extracellular signal-regulated kinase (ERK) 1/2, also referred to as p44/42 mitogen-activated protein kinase. Hypoplastic lungs had more elevated ERK 1/2 protein than normal developing lungs. Exposure to exogenous VEGF activated ERK 1/2 in normal developing lungs but not in hypoplastic lungs. Our results suggest that in hypoplastic lungs: 1) low VEGF signifies negative effects on vasculogenesis/angiogenesis and indicates altered endothelial-mesenchymal interactions; 2) increased ANG-1 protein may be required to maintain vessel integrity and quiescence; and 3) regulation of ERK 1/2 protein is affected in hypoplastic lungs. We speculate that extensive remodeling of blood vessels in hypoplastic lungs may occur to compensate for structurally and functionally defective vasculature. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|