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Open Access Highly Accessed Research article

Local erythropoietin and endothelial progenitor cells improve regional cardiac function in acute myocardial infarction

Andreas Stein1, Martina Knödler1, Markus Makowski3, Sandra Kühnel2, Stefan Nekolla3, Alexandra Keithahn3, Eliane Weidl2, Philip Groha1, Maren Schürmann2, Atti Saraste3, Rene Botnar3, Robert AJ Oostendorp2 and Ilka Ott1*

Author Affiliations

1 Deutsches Herzzentrum der Technischen Universität München, Lazarettstr. 36, 80636 München, Germany

2 Medizinische Klinik der Technischen Universität München, Ismaningerstr. 22, 81675 München, Germany

3 Nuklearmedizinische Klinik und Poliklinik der Technischen Universität München, Ismaningerstr. 22, 81675 München, Germany

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BMC Cardiovascular Disorders 2010, 10:43  doi:10.1186/1471-2261-10-43

Published: 17 September 2010

Abstract

Background

Expanded endothelial progenitor cells (eEPC) improve global left ventricular function in experimental myocardial infarction (MI). Erythropoietin beta (EPO) applied together with eEPC may improve regional myocardial function even further by anti-apoptotic and cardioprotective effects. Aim of this study was to evaluate intramyocardial application of eEPCs and EPO as compared to eEPCs or EPO alone in experimental MI.

Methods and Results

In vitro experiments revealed that EPO dosed-dependently decreased eEPC and leukocyte apoptosis. Moreover, in the presence of EPO mRNA expression in eEPC of proangiogenic and proinflammatory mediators measured by TaqMan PCR was enhanced. Experimental MI was induced by ligation and reperfusion of the left anterior descending coronary artery of nude rats (n = 8-9). After myocardial transplantation of eEPC and EPO CD68+ leukocyte count and vessel density were enhanced in the border zone of the infarct area. Moreover, apoptosis of transplanted CD31 + TUNEL + eEPC was decreased as compared to transplantation of eEPCs alone. Regional wall motion of the left ventricle was measured using Magnetic Resonance Imaging. After injection of eEPC in the presence of EPO regional wall motion significantly improved as compared to injection of eEPCs or EPO alone.

Conclusion

Intramyocardial transplantation of eEPC in the presence of EPO during experimental MI improves regional wall motion. This was associated with an increased local inflammation, vasculogenesis and survival of the transplanted cells. Local application of EPO in addition to cell therapy may prove beneficial in myocardial remodeling.