Erythropoietin preserves the endothelial differentiation capacity of cardiac progenitor cells and reduces heart failure during anticancer therapies

Anticancer therapies, such as targeting of STAT3 or the use of anthracyclins (doxorubicin), can induce cardiomyopathy. In mice prone to developing heart failure as a result of reduced cardiac STAT3 expression (cardiomyocyte-restricted deficiency of STAT3) or treatment with doxorubicin, we observed i...

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Veröffentlicht in:Cell stem cell Jg. 9; H. 2; S. 131
Hauptverfasser: Hoch, Melanie, Fischer, Philipp, Stapel, Britta, Missol-Kolka, Ewa, Sekkali, Belaid, Scherr, Michaela, Favret, Fabrice, Braun, Thomas, Eder, Matthias, Schuster-Gossler, Karin, Gossler, Achim, Hilfiker, Andres, Balligand, Jean-Luc, Drexler, Helmut, Hilfiker-Kleiner, Denise
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 05.08.2011
Schlagworte:
Adipocytes - cytology
Adipocytes - drug effects
Animals
Antigens, Ly - metabolism
Antineoplastic Agents - adverse effects
Capillaries - drug effects
Capillaries - pathology
Cell Differentiation - drug effects
Doxorubicin - pharmacology
Doxorubicin - therapeutic use
Endothelial Cells - cytology
Endothelial Cells - drug effects
Endothelial Cells - metabolism
Erythropoietin - pharmacology
Erythropoietin - therapeutic use
Fibroblasts - cytology
Fibroblasts - drug effects
Gene Deletion
Heart Failure - chemically induced
Heart Failure - drug therapy
Heart Failure - physiopathology
Heart Function Tests - drug effects
Humans
Membrane Proteins - metabolism
Mice
Mice, Knockout
Myocardium - pathology
Organ Specificity - drug effects
Pericytes - cytology
Pericytes - drug effects
Receptors, CCR2 - metabolism
Receptors, Erythropoietin - metabolism
STAT3 Transcription Factor - metabolism
Stem Cells - cytology
Stem Cells - drug effects
Stem Cells - metabolism
Survival Analysis
Vascular Endothelial Growth Factor Receptor-2 - metabolism
ISSN:1875-9777, 1875-9777
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Zusammenfassung:Anticancer therapies, such as targeting of STAT3 or the use of anthracyclins (doxorubicin), can induce cardiomyopathy. In mice prone to developing heart failure as a result of reduced cardiac STAT3 expression (cardiomyocyte-restricted deficiency of STAT3) or treatment with doxorubicin, we observed impaired endothelial differentiation capacity of Sca-1(+) cardiac progenitor cells (CPCs) in conjunction with attenuated CCL2/CCR2 activation. Mice in both models also displayed reduced erythropoietin (EPO) levels in the cardiac microenvironment. EPO binds to CPCs and seems to be responsible for maintaining an active CCL2/CCR2 system. Supplementation with the EPO derivative CERA in a hematocrit-inactive low dose was sufficient to upregulate CCL2, restore endothelial differentiation of CPCs, and preserve the cardiac microvasculature and cardiac function in both mouse models. Thus, low-dose EPO treatment could potentially be exploited as a therapeutic strategy to reduce the risk of heart failure in certain treatment regimens.
Bibliographie:ObjectType-Article-1
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ISSN:1875-9777
1875-9777
DOI:10.1016/j.stem.2011.07.001