Expression of angiogenic factor thymidine phosphorylase and angiogenesis in human atherosclerosis.
In atherosclerosis, leukocyte migration into the plaque is thought to occur across the endothelium of the arterial lumen. However, intraplaque microvessels have been noted. While the significance of, and stimuli for these are uncertain, it seems possible that they may represent a second portal of entry for leukocytes into the plaque. This study performed a basic characterization of intraplaque microvessels and tested the hypothesis that the novel angiogenic factor thymidine phosphorylase (TP) is expressed in atherosclerosis. Immunocytochemistry was performed on aortic and coronary plaques and morphometry on coronary plaques. In plaques from both sites, macrophages, foam cells, and giant cells were immunoreactive for the angiogenic factors TP and vascular endothelial growth factor. Venule-like intraplaque microvessels expressed endothelial leukocyte adhesion molecules HLA-DR and ICAM-1, in contrast to the endothelium overlying the plaque. In coronary plaques, there was a correlation between severity of stenosis and plaque microvascular density. These results are consistent with a role for plaque macrophage/foam cell TP in stimulating plaque angiogenesis. While attention has focused on dysfunction of the endothelium overlying the plaque, microvascular endothelium may also represent a portal of entry for leukocytes into established plaques.
Boyle
J J
JJ
Department of Medicine, Cambridge University, Cambridge, UK. jjb36@mole.bio.cam.ac.uk
Wilson
B
B
Bicknell
R
R
Harrower
S
S
Weissberg
P L
PL
Fan
T P
TP
D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology*; D003324:Coronary Artery Disease / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005487:Foam Cells / Q000378:metabolism; D015726:Giant Cells / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000201:enzymology*; D013939:Thymidine Phosphorylase / Q000378:metabolism*
D016228:Endothelial Growth Factors; D006684:HLA-DR Antigens; D018799:Intercellular Adhesion Molecule-1; D013939:Thymidine Phosphorylase