Heterogeneity of the Angiogenic Response Induced in Different Normal Adult Tissues by Vascular Permeability Factor/Vascular Endothelial Growth Factor
| Autor: | José Eduardo Krieger, Janice A. Nagy, Anna Pettersson, Carter R, Lawrence F. Brown, Richard C. Mulligan, Dian Feng, Ann M. Dvorak, Eleanor J. Manseau, Ellen S. Morgan, V. S. Harvey, Christian Sundberg, Harold F. Dvorak, I A Eckelhoefer, Jungles S |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Vascular Endothelial Growth Factor A
Pathology medicine.medical_specialty Angiogenesis Mice Nude Neovascularization Physiologic Adipose tissue Endothelial Growth Factors Biology Pathology and Forensic Medicine Capillary Permeability Neovascularization Mice chemistry.chemical_compound medicine Animals Molecular Biology Basement membrane Lymphokines Mice Inbred BALB C Vascular Endothelial Growth Factors Genetic transfer Cell Biology Anatomy Rats Endothelial stem cell Vascular endothelial growth factor medicine.anatomical_structure chemistry cardiovascular system Female Pericyte medicine.symptom |
| Zdroj: | Laboratory Investigation. 80:99-115 |
| ISSN: | 0023-6837 |
| DOI: | 10.1038/labinvest.3780013 |
| Popis: | Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) is an angiogenic cytokine with potential for the treatment of tissue ischemia. To investigate the properties of the new blood vessels induced by VPF/VEGF, we injected an adenoviral vector engineered to express murine VPF/VEGF164 into several normal tissues of adult nude mice or rats. A dose-dependent angiogenic response was induced in all tissues studied but was more intense and persisted longer (months) in skin and fat than in heart or skeletal muscle (or =3 weeks). The initial response (within 18 hours) was identical in all tissues studied and was characterized by microvascular hyperpermeability, edema, deposition of an extravascular fibrin gel, and the formation of enlarged, thin-walled pericyte-poor vessels ("mother" vessels). Mother vessels developed from preexisting microvessels after pericyte detachment and basement membrane degradation. Mother vessels were transient structures that evolved variably in different tissues into smaller daughter vessels, disorganized vessel tangles (glomeruloid bodies), and medium-sized muscular arteries and veins. Vascular structures closely resembling mother vessels and each mother vessel derivative have been observed in benign and malignant tumors, in other examples of pathological and physiological angiogenesis, and in vascular malformations. Together these data suggest that VPF/VEGF has a role in the pathogenesis of these entities. They also indicate that the angiogenic response induced by VPF/VEGF is heterogeneous and tissue specific. Finally, the muscular vessels that developed from mother vessels in skin and perimuscle fat have the structure of collaterals and could be useful clinically in the relief of tissue ischemia. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|