RGD Reference Report - Vascular endothelial growth factor is crucial for erythropoietin-induced improvement of cardiac function in heart failure. - Rat Genome Database

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Vascular endothelial growth factor is crucial for erythropoietin-induced improvement of cardiac function in heart failure.

Authors: Westenbrink, BD  Ruifrok, WP  Voors, AA  Tilton, RG  Van Veldhuisen, DJ  Schoemaker, RG  Van Gilst, WH  De Boer, RA 
Citation: Westenbrink BD, etal., Cardiovasc Res. 2010 Jul 1;87(1):30-9. doi: 10.1093/cvr/cvq041. Epub 2010 Feb 5.
RGD ID: 10401073
Pubmed: PMID:20139114   (View Abstract at PubMed)
DOI: DOI:10.1093/cvr/cvq041   (Journal Full-text)

AIMS: We intended to delineate the mechanisms of erythropoietin (EPO)-induced cardiac vascular endothelial growth factor (VEGF) production and to establish if VEGF is crucial for EPO-induced improvement of cardiac performance. METHODS AND RESULTS: The effects of EPO on VEGF expression were studied in cultured cardiac cells and EPO-treated hearts. The role of VEGF in EPO-induced neovascularization was studied with two distinct VEGF-neutralizing antibodies or irrelevant control IgG in an aortic sprouting assay and in rats with heart failure (HF) after myocardial infarction (MI) treated with EPO. EPO-alfa (10 IU/mL) was used in vitro and darbepoetin alfa (40 microg/kg/3 weeks, starting 3 weeks after MI) in vivo. EPO stimulated VEGF mRNA expression through the signal transducers and activators of transcription-3 (STAT-3) pathway in neonatal rat cardiomyocytes, but not in endothelial cells or fibroblasts. Similarly, the direct effects of EPO on endothelial sprouting were modest and VEGF independent. In rats with HF, EPO increased VEGF protein expression predominantly in cardiomyocytes, associated with a 37% increase in capillary density and improved cardiac performance. Administration of VEGF-neutralizing antibodies abrogated the salutary effects of EPO on cardiac microvascularization and function. VEGF neutralization attenuated EPO-induced proliferation of myocardial endothelial cells and reduced myocardial incorporation of endothelial progenitor cells (EPCs) in rats with alkaline phosphatase-labelled bone marrow cells. CONCLUSION: VEGF is crucial for EPO-induced improvement of cardiac function in HF. EPO fosters VEGF expression predominantly in cardiomyocytes, which in turn stimulates myocardial endothelial proliferation and incorporation of EPCs.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
congestive heart failure treatmentIDA 10401073associated with Myocardial InfarctionRGD 
congestive heart failure treatmentISOEPO (Homo sapiens)10401073; 10401073associated with Myocardial InfarctionRGD 

Objects Annotated

Genes (Rattus norvegicus)
Epo  (erythropoietin)

Genes (Mus musculus)
Epo  (erythropoietin)

Genes (Homo sapiens)
EPO  (erythropoietin)


Additional Information