Skip Navigation



Cardiovascular Research Advance Access [Accepted Manuscript] published online on November 18, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn312
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
81/2/310    most recent
cvn312v2
cvn312v1
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 Meyer-Kirchrath, J.
Right arrow Articles by Hohlfeld, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Meyer-Kirchrath, J.
Right arrow Articles by Hohlfeld, T.
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.

Overexpression of prostaglandin EP3 receptors activates calcineurin and promotes hypertrophy in the murine heart

Jutta Meyer-Kirchrath, PhD1, Melanie Martin, PhD1, Christina Schooss, BSc1, Christoph Jacoby, PhD2, Ulrich Flögel, PhD2, Andrea Marzoll, BSc1, Jens W. Fischer, PhD1, Jürgen Schrader, MD2, Karsten Schrör, MD1 and Thomas Hohlfeld, MD1

1 Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität, Düsseldorf, Germany
2 Institut für Herz- und Kreislaufphysiologie, Heinrich-Heine-Universität, Düsseldorf, Germany

Address for correspondence: Jutta Meyer-Kirchrath, Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum, Heinrich-Heine-Universität, Moorenstr. 5, D-40225 Düsseldorf, Germany, Phone (+49-211) 81-12500, Fax: (+49-211) 81-14781, e-mail: meyerj{at}uni-duesseldorf.de

Aims: Prostaglandin E2 (PGE2) has been shown to mediate anti-ischemic effects and cardiomyocyte hypertrophy and there is evidence for an involvement of the prostaglandin EP3 receptor subtype. This study focuses on the EP3-mediated hypertrophic action and investigates intracellular signaling pathways of the EP3 receptor subtype in the murine heart.

Methods: Cardiac function was analyzed in vivo by magnetic resonance imaging (MRI) in transgenic (tg) mice with cardio-specific overexpression of the EP3 receptor in comparison with wild-type (wt) mice. Left ventricular (LV) function was determined in isolated perfused hearts subjected to 60 min of zero-flow ischemia and 45 min of reperfusion. Calcineurin activity and nuclear activity of nuclear factor of activated T-cells (NFAT) were determined by a modified malachite green assay and ELISA, respectively. Extracellular matrix compounds were analyzed by RT-PCR and histology.

Results: MRI indicated a significant increase in end-diastolic and end-systolic volume in tg hearts. LV ejection fraction was severely decreased in tg hearts while the relative LV mass was significantly increased. In Langendorff perfused hearts, EP3 receptor overexpression resulted in a marked blunting of the ischemia-induced increase in LV end-diastolic pressure (LVEDP) and creatine kinase (CK) release. Analysis of EP3 receptor-mediated signaling revealed significantly increased calcineurin activity and nuclear activity of NFAT in tg hearts. Moreover, elevated mRNA levels of collagen types I and III as well as the collagen-binding proteoglycans biglycan and decorin were detected in tg hearts.

Conclusion: EP3 receptor-mediated signaling results in a significant anti-ischemic action and activation of the pro-hypertrophic calcineurin signaling pathway, suggesting the involvement of the EP3 subtype in both PGE2-mediated cardioprotection as well as cardiac hypertrophy.

KEYWORDS calcineurin; hypertrophy; NFAT; prostaglandins; EP3 receptor

Time for primary review: 41 Days


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.