Skip Navigation


Cardiovascular Research Advance Access first published online on September 20, 2008
This version [Corrected Proof] published online on October 3, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn251
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
81/1/28    most recent
cvn251v2
cvn251v1
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 Urayama, K.
Right arrow Articles by Nebigil, C. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Urayama, K.
Right arrow Articles by Nebigil, C. G.
Related Collections
Right arrowRelated Article
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.

Transgenic myocardial overexpression of prokineticin receptor-2 (GPR73b) induces hypertrophy and capillary vessel leakage

Kyoji Urayama1, Deniz B. Dedeoglu1, Célia Guilini1, Stefan Frantz2, Georg Ertl2, Nadia Messaddeq3 and Canan G. Nebigil1,*

1 CNRS/ULP, UMR 7175-LC1, Ecole Supérieure de Biotechnologie de Strasbourg, Bld. Sébastien Brandt BP. 10413, F-67412 Illkirch, France
2 Medizinsche Klinik und Poliklinik I, Herz-/Kreislaufzentrum, University Wurzburg, Wurzburg, Germany
3 Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/ULP UMR 7104, INSERM U596, BP. 10142, F-67404 Illkirch, France

* Corresponding author. Tel: +33 390 24 47 56; fax: +33 390 24 48 29. E-mail address: nebigil{at}esbs.u-strasbg.fr

Aims: Prokineticins are small secreted bioactive molecules. They exert their biological activity by binding to two G protein-coupled receptors. Previously, we have shown that the overexpression of prokineticin receptor-1 (PKR1) in transgenic (TG) mouse hearts induced neovascularization. Since PKR1 and PKR2 are 85% identical and expressed in cardiovascular tissues, we hypothesized that PKR2 may also contribute to cardiomyocyte growth and vascularization.

Methods and results: We have generated TG mice overexpressing PKR2 in cardiomyocytes. TG mice exhibit increased hypertrophic gene expression and heart-to-body weight ratio accompanied by an increased length of cardiomyocytes at the age of 12 weeks. Increased left ventricular end-systolic and diastolic diameters without cardiac dysfunction at the age of 24 weeks indicate that TG mice have an eccentric hypertrophy with compensated cardiac function. Quantitative morphological analysis showed that TG hearts have a normal microvessel density and number of branch points. However, they exhibit increased abnormal endothelial cell shape and ultrastructure, changed cellular distribution of a tight junction protein zona occludens-1 (ZO-1), and vascular leakage in heart without a rise of angiogenic factor levels at early and late age. The application of media conditioned by H9c2 cardioblast cells overexpressing PKR2 significantly induced impaired ZO-1 localization in H5V endothelial cells, mimicking the TG model.

Conclusion: These findings provide the first genetic evidence that cardiomyocyte PKR2 signalling leads to eccentric hypertrophy in an autocrine regulation and impaired endothelial integrity in a paracrine regulation without inducing angiogenesis. These TG mice may provide a new genetic model for heart diseases.

KEYWORDS GPCR; Prokineticin; Fenestration; Transgenic mice; Cardiomyocyte; ZO-1

Time for primary review: 33 days


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

Related Article

Prokineticins and the heart: diverging actions elicited by signalling through prokineticin receptor-1 or -2
Håvard Attramadal
Cardiovasc Res 2009 81: 3-4. [Extract] [Full Text] [PDF]



This article has been cited by other articles:


Home page
 J. Appl. Physiol.Home page
R. D. Rudic and D. J. Fulton
Pressed for time: the circadian clock and hypertension
J Appl Physiol, October 1, 2009; 107(4): 1328 - 1338.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
H. Attramadal
Prokineticins and the heart: diverging actions elicited by signalling through prokineticin receptor-1 or -2
Cardiovasc Res, January 1, 2009; 81(1): 3 - 4.
[Full Text] [PDF]


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.