Skip Navigation


Cardiovascular Research Advance Access originally published online on November 20, 2007
Cardiovascular Research 2008 77(3):580-589; doi:10.1093/cvr/cvm076
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
77/3/580    most recent
cvm076v2
cvm076v1
Right arrow Alert me when this article is cited
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 ISI Web of Science
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
Google Scholar
Right arrow Articles by Nührenberg, T. G.
Right arrow Articles by Zohlnhöfer, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nührenberg, T. G.
Right arrow Articles by Zohlnhöfer, D.
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 2007. For permissions please email: journals.permissions@oxfordjournals.org

EMAP-II downregulation contributes to the beneficial effects of rapamycin after vascular injury

Thomas G. Nührenberg1,{dagger}, Nicolas Langwieser1,{dagger}, Johannes B.K. Schwarz1, Yonghao Hou2, Pamela Frank1,5, Falko Sorge1, Susanne Matschurat3, Stefan Seidl4, Adnan Kastrati1, Albert Schömig1, Matthias A. Clauss2 and Dietlind Zohlnhöfer1,*

1 Klinik für Herz- und Kreislaufkrankheiten, I. Medizinische Klinik und Deutsches Herzzentrum der Technischen Universität München, Lazarettstr. 36, D-80636 München, Germany
2 Indiana Center for Vascular Biology & Medicine, Indianapolis, USA
3 formerly Molekulare Zellbiologie, Max-Plank-Institut für Herz- und Lungenforschung, Bad Nauheim, Germany
4 Institut für Pathologie, Germany
5 Institut für experimentelle Chirurgie Germany

* Corresponding author. Tel: +49 89 1218 4012; fax: +49 89 1218 4013. E-mail address: d_zohlnhoefer{at}yahoo.com

Aims: Neointima formation after vascular injury is strongly associated with inflammation. Rapamycin inhibits human neointima formation and reduces expression of the proinflammatory cytokine endothelial-monocyte activating peptide II (EMAP-II) in vitro. Here we investigated the interplay between EMAP-II and rapamycin after vascular injury in vivo.

Methods and results: In a mouse model of vascular injury, mice were either not treated, given everolimus, a rapamycin derivate, or subjected to simultaneous challenge with everolimus and EMAP-II. EMAP-II expression was measured in coronary artery smooth muscle cells (CASMC) and monocytic cells in vitro and in patients after percutaneous coronary intervention (PCI). After vascular injury, rapamycin reduced neointima formation and adventitial thickening. Immunohistochemistry revealed reduced EMAP-II protein expression and suppressed recruitment of inflammatory cells. Simultaneous challenge with EMAP-II counteracted these effects of rapamycin. Expression of EMAP-II and its inhibition by rapamycin was confirmed in CASMC and monocytic cells. In patients, EMAP-II upregulation was confined to PCI of distal coronary artery segments and profoundly suppressed by oral rapamycin treatment.

Conclusion: These data suggest important yet unrecognized roles of EMAP-II and adventitial inflammation in neointima formation: Through inhibition of EMAP-II, rapamycin reduces the recruitment of inflammatory cells to the adventitia and supports an early and bland healing.

KEYWORDS Restenosis; Inflammation; Adventitia; Endothelium; Drugs

Time for primary review: 25 days

{dagger} These authors contributed equally to this work.


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.