Skip Navigation



Cardiovascular Research Advance Access [Accepted Manuscript] published online on June 19, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp178
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
84/1/54    most recent
cvp178v2
cvp178v1
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 Zhou, Y.
Right arrow Articles by Kang, Y. J.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhou, Y.
Right arrow Articles by Kang, Y. J.
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 2009. For permissions please email: journals.permissions@oxfordjournals.org.

Copper-induced Regression of Cardiomyocyte Hypertrophy Is Associated with Enhanced VEGF Receptor-1 Signaling Pathway

Yang Zhou1, Katherine Bourcy1 and Y. James Kang1,2

1 Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky 40202
2 Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China

Correspondence address: Dr. Y. James Kang, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China, E-mail: yjkang01{at}louisville.edu

Aims: Vascular endothelial growth factor (VEGF) has been well documented to stimulate cell proliferation and differentiation; however, we have observed that copper-induced regression of heart hypertrophy was VEGF dependent. The present study was undertaken to test the hypothesis that copper causes alterations in the distribution of VEGF receptors in hypertrophic cardiomyocytes so that it switches the signaling pathway from stimulation of cell growth to reversal of cell hypertrophy.

Methods: Primary cultures of neonatal rat cardiomyocytes were exposed to phenylephrine (PE) at a final concentration of l00 µM in cultures for 48 h to induce cell hypertrophy. The hypertrophic cardiomyocytes were exposed to copper sulfate at a final concentration of 5 µM in cultures for 24 h with a concomitant presence of PE. Flow cytometry, gene silencing, and ELISA procedures were used to analyze the changes in VEGF receptors and their relationship with regression of cardiomyocyte hypertrophy.

Results: Copper did not change the concentration of VEGF in culture media, but increased the ratio of VEGF receptor-1 (VEGFR-1) to VEGF receptor-2 (VEGFR-2) twofold. Gene silencing of VEGFR-2, in the absence of copper addition, reversed PE-induced cardiomyocyte hypertrophy, which was suppressed by an anti-VEGF antibody. Gene silencing of VEGFR-1 blocked copper-induced regression of cell hypertrophy and decreased the activity of cGMP-dependent protein kinase-1 (PKG-1). A PKG-1 antagonist, Rp-8-pCPT-cGMPS, blocked both copper- and VEGFR-2 gene silencing-induced regression of cardiomyocyte hypertrophy.

Conclusions: Enhanced VEGFR-1 signaling is involved in copper regression of cardiomyocyte hypertrophy, and the PKG-1 pathway is likely associated with VEGFR-1.

Time for primary review: 25 Days


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

Related Article

VEGF receptor switching in heart development and disease
Rosalinda Madonna and Raffaele De Caterina
Cardiovasc Res 2009 84: 4-6. [Extract] [Full Text] [PDF]



This article has been cited by other articles:


Home page
 Cardiovasc ResHome page
R. Madonna and R. De Caterina
VEGF receptor switching in heart development and disease
Cardiovasc Res, October 1, 2009; 84(1): 4 - 6.
[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.