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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Hellström, M. Wolburg, H. Betsholtz, C. Eriksson, U. Gerhardt, H. Kalén, M. Li, X. |
| Description | Author Affiliation: Hellström M ( Department of Medical Biochemistry, Göteborg University, SE-405 30 Göteborg, Sweden.) |
| Abstract | The association of pericytes (PCs) to newly formed blood vessels has been suggested to regulate endothelial cell (EC) proliferation, survival, migration, differentiation, and vascular branching. Here, we addressed these issues using PDGF-B– and PDGF receptor-β (PDGFR-β)–deficient mice as in vivo models of brain angiogenesis in the absence of PCs. Quantitative morphological analysis showed that these mutants have normal microvessel density, length, and number of branch points. However, absence of PCs correlates with endothelial hyperplasia, increased capillary diameter, abnormal EC shape and ultrastructure, changed cellular distribution of certain junctional proteins, and morphological signs of increased transendothelial permeability. Brain endothelial hyperplasia was observed already at embryonic day (E) 11.5 and persisted throughout development. From E 13.5, vascular endothelial growth factor-A (VEGF-A) and other genes responsive to metabolic stress became upregulated, suggesting that the abnormal microvessel architecture has systemic metabolic consequences. VEGF-A upregulation correlated temporally with the occurrence of vascular abnormalities in the placenta and dilation of the heart. Thus, although PC deficiency appears to have direct effects on EC number before E 13.5, the subsequent increased VEGF-A levels may further abrogate microvessel architecture, promote vascular permeability, and contribute to formation of the edematous phenotype observed in late gestation PDGF-B and PDGFR-β knock out embryos. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 3 |
| Volume Number | 153 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 2001-04-30 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Blood Vessels Pathology Endothelium, Vascular Neovascularization, Pathologic Pericytes Animals Antigens, CD Aquaporin 4 Aquaporins Isolation & Purification Embryology Brain Blood Supply Brain Chemistry Cadherins Capillaries Ultrastructure Capillary Permeability Caveolae Caveolin 1 Caveolins Endothelial Growth Factors Gene Expression Regulation Hyperplasia Liver Chemistry Membrane Proteins Mice Mice, Knockout Mice, Mutant Strains Microscopy, Confocal Models, Biological Morphogenesis Occludin Platelet-Derived Growth Factor Genetics Receptor, Platelet-Derived Growth Factor Beta Tight Junctions Vascular Endothelial Growth Factor A Research Support, Non-U.S. Gov't Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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