Lymphangiogenic Growth Factor Responsiveness Is Modulated by Postnatal Lymphatic Vessel Maturation
| Autor: | Taija Makinen, Terhi Karpanen, Marc G. Achen, Hidde J. Haisma, Bronislaw Pytowski, Kari Alitalo, Tanja Veikkola, Steven A. Stacker, Seppo Ylä-Herttuala, Maria Wirzenius |
|---|---|
| Přispěvatelé: | Biopharmaceuticals, Discovery, Design and Delivery (BDDD) |
| Rok vydání: | 2006 |
| Předmět: |
Pathology
medicine.medical_specialty medicine.medical_treatment Vascular Endothelial Growth Factor C Vascular Endothelial Growth Factor D Biology Ligands Adenoviridae Pathology and Forensic Medicine Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Lymphatic vessel medicine Animals Humans Regeneration Transgenes Lymphangiogenesis Lymph sacs Growth Substances Lymphatic Vessels 030304 developmental biology 0303 health sciences Hyperplasia Growth factor Newborn Vascular Endothelial Growth Factor Receptor-3 Vascular endothelial growth factor medicine.anatomical_structure Lymphatic system Animals Newborn Solubility Vascular endothelial growth factor C chemistry 030220 oncology & carcinogenesis Immunology Commentary cardiovascular system |
| Zdroj: | American Journal of Pathology, 169(2), 708-718. ELSEVIER SCIENCE INC |
| ISSN: | 0002-9440 |
| DOI: | 10.2353/ajpath.2006.051200 |
| Popis: | Lymphatic vessel plasticity and stability are of considerable importance when attempting to treat diseases associated with the lymphatic vasculature. Development of lymphatic vessels during embryogenesis is dependent on vascular endothelial growth factor (VEGF)-C but not VEGF-D. Using a recombinant adenovirus encoding a soluble form of their receptor VEGFR-3 (AdVEGFR-3-Ig), we studied lymphatic vessel dependency on VEGF-C and VEGF-D induced VEGFR-3 signaling in postnatal and adult mice. Transduction with AdVEGFR-3-Ig led to regression of lymphatic capillaries and medium-sized lymphatic vessels in mice under 2 weeks of age without affecting collecting lymphatic vessels or the blood vasculature. No effect was observed after this period. The lymphatic capillaries of neonatal mice also regressed partially in response to recombinant VEGFR3-Ig or blocking antibodies against VEGFR-3, but not to adenovirus-encoded VEGFR-2-Ig. Despite sustained inhibitory VEGFR-3-Ig levels, lymphatic vessel regrowth was observed at 4 weeks of age. interestingly, whereas transgenic expression of VEGF-C in the skin induced lymphatic hyperplasia even during embryogenesis, similar expression of VEGF-D resulted in lymphangio-genesis predominantly after birth. These results indicate considerable plasticity of lymphatic vessels during the early postnatal period but not thereafter, suggesting that anti-lymphangiogenic therapy can he safely applied in adults. |
| Databáze: | OpenAIRE |
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