|
|
|
|
|
|
|
||
© The Rockefeller University Press,
0021-9525/2001//543 $5.00
The Journal of Cell Biology, Volume 153, Number 3,
, 2001 543-554
Original Article |
Lack of Pericytes Leads to Endothelial Hyperplasia and Abnormal Vascular Morphogenesis
christer.betsholtz{at}medkem.gu.se
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.
Key Words: mice • angiogenesis • pericytes • platelet-derived growth factor B • vascular endothelial growth factor
© 2001 The Rockefeller University Press
Abbreviations used in this paper: E, embryonic day; EC, endothelial cell; Glut-1, glucose transporter 1; LDH, lactate dehydrogynase; PC, pericyte; PDGFR-β, PDGF receptor-β; PGK, phosphoglycerate kinase; VEGF-A, vascular endothelial growth factor-A; vSMC, vascular smooth muscle cell.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
|
|
