RGD Reference Report - Copper-induced regression of cardiomyocyte hypertrophy is associated with enhanced vascular endothelial growth factor receptor-1 signalling pathway. - Rat Genome Database

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Copper-induced regression of cardiomyocyte hypertrophy is associated with enhanced vascular endothelial growth factor receptor-1 signalling pathway.

Authors: Zhou, Y  Bourcy, K  Kang, YJ 
Citation: Zhou Y, etal., Cardiovasc Res. 2009 Oct 1;84(1):54-63. doi: 10.1093/cvr/cvp178. Epub 2009 Jun 19.
RGD ID: 7775063
Pubmed: PMID:19542178   (View Abstract at PubMed)
PMCID: PMC2741345   (View Article at PubMed Central)
DOI: DOI:10.1093/cvr/cvp178   (Journal Full-text)

AIMS: Vascular endothelial growth factor (VEGF) has been well documented to stimulate cell proliferation and differentiation; however, we have observed that copper (Cu)-induced regression of heart hypertrophy was VEGF-dependent. The present study was undertaken to test the hypothesis that Cu causes alterations in the distribution of VEGF receptors (VEGFRs) in hypertrophic cardiomyocytes so that it switches the signalling pathway from stimulation of cell growth to reversal of cell hypertrophy. METHODS AND RESULTS: Primary cultures of neonatal rat cardiomyocytes were exposed to phenylephrine (PE) at a final concentration of 100 microM in cultures for 48 h to induce cell hypertrophy. The hypertrophic cardiomyocytes were exposed to copper sulfate at a final concentration of 5 microM in cultures for 24 h with a concomitant presence of PE. Flow cytometry, gene silencing, and ELISA procedures were used to analyse the changes in VEGFRs and their relationship with regression of cardiomyocyte hypertrophy. Cu did not change the concentration of VEGF in culture media, but increased the ratio of VEGFR-1 to VEGFR-2 two-fold. Gene silencing of VEGFR-2, in the absence of Cu addition, reversed PE-induced cardiomyocyte hypertrophy, which was suppressed by an anti-VEGF antibody. Gene silencing of VEGFR-1 blocked Cu-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 Cu- and VEGFR-2 gene silencing-induced regression of cardiomyocyte hypertrophy. CONCLUSION: Enhanced VEGFR-1 signalling is involved in Cu regression of cardiomyocyte hypertrophy, and the PKG-1 pathway is likely associated with VEGFR-1.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cell growth involved in cardiac muscle cell development  IMP 7775063 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Prkg1  (protein kinase cGMP-dependent 1)


Additional Information