Skip Navigation


Cardiovascular Research Advance Access first published online on February 21, 2009
This version [Corrected Proof] published online on March 14, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp065
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
83/2/381    most recent
cvp065v3
cvp065v2
cvp065v1
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 Kasseckert, S. A.
Right arrow Articles by Abdallah, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kasseckert, S. A.
Right arrow Articles by Abdallah, Y.
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 2009. For permissions please email: journals.permissions@oxfordjournals.org.

Stimulation of cGMP signalling protects coronary endothelium against reperfusion-induced intercellular gap formation

Sascha A. Kasseckert, Claudia Schäfer, Angelika Kluger, Dragan Gligorievski, Julia Tillmann, Klaus-Dieter Schlüter, Thomas Noll, Heinrich Sauer, Hans Michael Piper and Yaser Abdallah*

Institute of Physiology, Justus Liebig University, Aulweg 129, D-35392 Giessen, Germany

* Corresponding author. Tel: +49 6419947223; fax: +49 6419947219. E-mail address: yaser.abdallah{at}physiologie.med.uni-giessen.de

Aims: Ischaemia–reperfusion provokes intercellular gap formation of the coronary microvasculature, impeding functional recovery of the heart during reperfusion. The aim of the present study was to investigate whether the stimulation of cGMP signalling by activation of soluble guanylyl cyclase (sGC) can reduce reperfusion-induced endothelial barrier failure and to determine whether this is due to an influence on endothelial cytosolic Ca2+ homeostasis during reperfusion.

Methods and results: Experiments were performed with cultured coronary endothelial monolayers and isolated saline-perfused rat hearts. HMR1766 (1 µmol/L) or DEAnonoate (0.5 µmol/L) were used to activate sGC. After exposure to simulated ischaemic conditions, reperfusion of endothelial cells led to a pronounced increase in cytosolic calcium levels and intercellular gaps. Stimulation of cGMP signalling during reperfusion increased Ca2+ sequestration in the endoplasmic reticulum (ER) and attenuated the reperfusion-induced increase in cytosolic [Ca2+]. Phosphorylation of phospholamban was also increased, indicating a de-inhibition of the ER Ca2+ pump (SERCA). Reperfusion-induced intercellular gap formation was reduced. Reduction of myosin light chain phosphorylation indicated inactivation of the endothelial contractile machinery. Effects on cytsolic Ca2+ and gaps were abrogated by inhibition of cGMP-dependent protein kinase (PKG) with KT5823. In reperfused hearts, stimulation of cGMP signalling led to decreased oedema development.

Conclusion: sGC/PKG activation during reperfusion reduces reperfusion-induced endothelial intercellular gap formation by attenuation of cytosolic calcium overload and reduction of contractile activation in endothelial cells. This mechanism protects the heart against reperfusion-induced oedema.

KEYWORDS Reperfusion injury; Endothelium; Nitric oxide; cGMP; Protein kinase G

Time for primary review: 26 days

This paper was guest edited by Hiroshi Watanabe, Hamamatsu University School of Medicine.


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.