Vascular Permeability Factor/Vascular Endothelial Growth Factor Induces Lymphangiogenesis as well as Angiogenesis
| Autor: | Xiaolian Tan, Janice A. Nagy, Dian Feng, Eliza Vasile, Ann M. Dvorak, Christian Sundberg, Harold F. Dvorak, Michael Detmar, Joel A. Lawitts, Laura E. Benjamin, Eleanor J. Manseau, Lawrence F. Brown |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2002 |
| Předmět: |
VPF/VEGF
Vascular Endothelial Growth Factor A Pathology medicine.medical_specialty Lymphoma Angiogenesis Immunology VEGF-C Endothelial Growth Factors VEGF-D Article VEGF-A Adenoviridae Neovascularization Lymphatic System 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine medicine Immunology and Allergy Animals 030304 developmental biology 0303 health sciences Lymphokines Neovascularization Pathologic business.industry Vascular Endothelial Growth Factors Vascular Endothelial Growth Factor D Vascular Endothelial Growth Factor Receptor-2 3. Good health Lymphangiogenesis Vascular endothelial growth factor Vascular endothelial growth factor A chemistry Vascular endothelial growth factor C PlGF 030220 oncology & carcinogenesis Lymphatic Metastasis Intercellular Signaling Peptides and Proteins Angiogenesis Inducing Agents Female medicine.symptom business Thymidine |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF, VEGF-A) is a multifunctional cytokine with important roles in pathological angiogenesis. Using an adenoviral vector engineered to express murine VEGF-A164, we previously investigated the steps and mechanisms by which this cytokine induced the formation of new blood vessels in adult immunodeficient mice and demonstrated that the newly formed blood vessels closely resembled those found in VEGF-A–expressing tumors. We now report that, in addition to inducing angiogenesis, VEGF-A164 also induces a strong lymphangiogenic response. This finding was unanticipated because lymphangiogenesis has been thought to be mediated by other members of the VPF/VEGF family, namely, VEGF-C and VEGF-D. The new “giant” lymphatics generated by VEGF-A164 were structurally and functionally abnormal: greatly enlarged with incompetent valves, sluggish flow, and delayed lymph clearance. They closely resembled the large lymphatics found in lymphangiomas/lymphatic malformations, perhaps implicating VEGF-A in the pathogenesis of these lesions. Whereas the angiogenic response was maintained only as long as VEGF-A was expressed, giant lymphatics, once formed, became VEGF-A independent and persisted indefinitely, long after VEGF-A expression ceased. These findings raise the possibility that similar, abnormal lymphatics develop in other pathologies in which VEGF-A is overexpressed, e.g., malignant tumors and chronic inflammation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|