Skip Navigation


Cardiovascular Research Advance Access first published online on September 18, 2008
This version [Corrected Proof] published online on October 1, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn256
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
81/1/187    most recent
cvn256v2
cvn256v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Rohlena, J.
Right arrow Articles by Horrevoets, A. J.G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rohlena, J.
Right arrow Articles by Horrevoets, A. J.G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org.

Endothelial CD81 is a marker of early human atherosclerotic plaques and facilitates monocyte adhesion

Jakub Rohlena1,{dagger}, Oscar L. Volger2, Jaap D. van Buul3, Liesbeth H.P. Hekking4, Janine M. van Gils3, Peter I. Bonta1, Ruud D. Fontijn2, Jan Andries Post4, Peter L. Hordijk3 and Anton J.G. Horrevoets2,*

1 Department of Medical Biochemistry, Academic Medical Centre, Amsterdam, The Netherlands
2 Department of Molecular Cell Biology and Immunology, VU University Medical Center, Room FG-B244, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands
3 Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, Amsterdam, The Netherlands
4 Department of Cell Biology, Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands

* Corresponding author. Tel: +31 20 4448161; fax: +31 20 4448081. E-mail address: aj.horrevoets{at}vumc.nl

Aims: In a recent report, we established at the genome-wide level those genes that are specifically upregulated in the endothelium of atherosclerotic plaques in human arteries. As the transcriptome data revealed that mRNA for the tetraspanin family member CD81 is significantly and specifically upregulated in the endothelium overlying early atheroma, we set out to validate these results on the protein level, and investigate the functional consequences of CD81 upregulation.

Methods and results: Immunohistochemical analysis in an independent set of donor arteries verified in the endothelium of early human atherosclerotic lesions the enhanced expression of CD81, which appears oxidative stress-dependent. Using lentiviral overexpression and silencing in human umbilical endothelial cells, we established in an in vitro flow adhesion assay that elevated endothelial CD81 is associated with increased monocyte adhesion to non-activated CD81-transduced endothelial cells, approaching the levels normally only attained after tumour necrosis factor {alpha} stimulation. The CD81 effect was dependent on both intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), as it was abolished in the presence of a mixture of anti-ICAM-1 and anti-VCAM-1 antibodies. Flow cytometry revealed that increased CD81 levels did not increase total ICAM-1 and VCAM-1 surface expression. Instead, it concentrated the available adhesion molecules into membrane clusters, as indicated by confocal and electron microscopy. CD81 also colocalized with ICAM-1 and VCAM-1 in the adhesion rings around bound monocytes.

Conclusion: Endothelial CD81 upregulated in early human atheroma has the potential to play a crucial role in the initial stages of atherosclerotic plaque formation by increasing monocyte adhesion prior to the full-blown inflammatory response.

KEYWORDS Endothelium; Atherosclerosis; Adhesion molecules

Time for primary review: 23 days

{dagger} Present address. Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.