Neovascular expression of VE-cadherin in human atherosclerotic arteries and its relation to intimal inflammation

Objective: The present work aimed to investigate how the Ca2+-dependent cel l adhesion molecule vascular endothelial (VE)-cadherin might be involved in atherogenesis. Methods: Specimens of human carotid artery and aorta were o btained at operation. An immunohistochemical approach using cell-type speci fic antibodies examined how VE-cadherin expression in areas of neovasculari sation related to the accumulation of immunocompetent and inflammatory cell s within atherosclerotic plaque. Electron microscopy was used to examine th e 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 th e outer third of the media. Within the atherosclerotic arterial segments, V E-cadherin was expressed in all layers of the arterial wall including the i ntima where VE-cadherin was expressed by endothelial cells in areas of neov ascularisation. In some neovessels, loss of VE-cadherin expression was asso ciated with increased focal accumulation of T-cells, macrophages and dendri tic 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 penetra tion of blood cells through patent intercellular zones. Conclusions: VE-cad herin is expressed in atherosclerotic lesions by endothelial cells associat ed with neovascularisation. Downregulation of VE-cadherin expression within some intimal neovessels is accompanied by increased entry of immunocompete nt cells into the intimal matrix surrounding areas of neovascularisation wh ich suggests that disorganising endothelial cell-to-cell interactions withi n neovessels is significant in atherogenesis. (C) 1999 Elsevier Science B.V . All rights reserved.