Neovascular expression of VE-cadherin in human atherosclerotic arteries and its relation to intimal inflammation.
OBJECTIVE
The present work aimed to investigate how the Ca(2+)-dependent cell adhesion molecule vascular endothelial (VE)-cadherin might be involved in atherogenesis.


METHODS
Specimens of human carotid artery and aorta were obtained at operation. An immunohistochemical approach using cell-type specific antibodies examined how VE-cadherin expression in areas of neovascularisation related to the accumulation of immunocompetent and inflammatory cells within atherosclerotic plaque. Electron microscopy was used to examine the structural characteristics of neovessels and the cell composition in the surrounding intimal matrix.


RESULTS
In all the non-atherosclerotic aortic segments, VE-cadherin expression was observed only in the adventitia and the outer third of the media. Within the atherosclerotic arterial segments, VE-cadherin was expressed in all layers of the arterial wall including the intima where VE-cadherin was expressed by endothelial cells in areas of neovascularization. In some neovessels, loss of VE-cadherin expression was associated with increased focal accumulation of T-cells, macrophages and dendritic cells. Electron-microscopic examination demonstrated varying degrees of endothelial continuity in the intimal neovessels. Within those neovessels which were surrounded by a large number of immunocompetent and inflammatory cells, some inter-endothelial cell contacts were open allowing the penetration of blood cells through patent intercellular zones.


CONCLUSIONS
VE-cadherin is expressed in atherosclerotic lesions by endothelial cells associated with neovascularisation. Downregulation of VE-cadherin expression within some intimal neovessels is accompanied by increased entry of immunocompetent cells into the intimal matrix surrounding areas of neovascularization which suggests that disorganizing endothelial cell-to-cell interactions within neovessels is significant in atherogenesis.
Bobryshev
Y V
YV
Surgical Professorial Unit, St. Vincent's Hospital, Darlinghurst NSW, Australia.
Cherian
S M
SM
Inder
S J
SJ
Lord
R S
RS
D000328:Adult; D000368:Aged; D015703:Antigens, CD; D001011:Aorta / Q000276:immunology / Q000648:ultrastructure; D001161:Arteriosclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015820:Cadherins / Q000032:analysis / Q000378:metabolism*; D002339:Carotid Arteries / Q000276:immunology / Q000648:ultrastructure; D003713:Dendritic Cells / Q000473:pathology; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000473:pathology; D008854:Microscopy, Electron; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology; D017539:Tunica Intima / Q000276:immunology / Q000378:metabolism; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D000099152:Cadherin 5