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. 2010 Sep 17:10:43.
doi: 10.1186/1471-2261-10-43.

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

Andreas Stein  1 , Martina Knödler, Markus Makowski, Sandra Kühnel, Stefan Nekolla, Alexandra Keithahn, Eliane Weidl, Philip Groha, Maren Schürmann, Atti Saraste, Rene Botnar, Robert Aj Oostendorp, Ilka Ott
Affiliations

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

Andreas Stein et al. BMC Cardiovasc Disord. .

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.

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Figures

Figure 1
Figure 1
Pretreatment with EPO dose dependently enhanced survival of leukocytes after serum starvation. (a, b) Stimulation of eEPC with EPO induced enhanced expression of proangiogenic and proinflammatory factors. (c)
Figure 2
Figure 2
Regional wall thickening measured in MRI of left ventricle and of infarct border zone (a) after alignment of MRI short axis plane (b) and histologic section (c).
Figure 3
Figure 3
No difference in global ejection fraction was seen between control and treatment groups. (a) Application of eEPC + EPO results in an improved regional cardiac function in the infarct border zone (b) and results in increased neovascularization (c)
Figure 4
Figure 4
Application of eEPC + EPO enhances recruitment of CD68+ cells to the infarct border zone (a) and reduces the number of apoptotic eEPCs (b) determined as double positive for human CD31 and TUNEL in immunofluorescence.
See this image and copyright information in PMC

References

    1. Leone AM, Rutella S, Bonanno G, Abbate A, Rebuzzi AG, Giovannini S, Lombardi M, Galiuto L, Liuzzo G, Andreotti F. et al.Mobilization of bone marrow-derived stem cells after myocardial infarction and left ventricular function. Eur Heart J. 2005;26(12):1196–1204. doi: 10.1093/eurheartj/ehi164. - DOI - PubMed
    1. Massa M, Rosti V, Ferrario M, Campanelli R, Ramajoli I, Rosso R, De Ferrari GM, Ferlini M, Goffredo L, Bertoletti A. et al.Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infarction. Blood. 2005;105(1):199–206. doi: 10.1182/blood-2004-05-1831. - DOI - PubMed
    1. Wojakowski W, Tendera M, Michalowska A, Majka M, Kucia M, Maslankiewicz K, Wyderka R, Ochala A, Ratajczak MZ. Mobilization of CD34/CXCR4+, CD34/CD117+, c-met+ stem cells, and mononuclear cells expressing early cardiac, muscle, and endothelial markers into peripheral blood in patients with acute myocardial infarction. Circulation. 2004;110(20):3213–3220. doi: 10.1161/01.CIR.0000147609.39780.02. - DOI - PubMed
    1. Calvillo L, Latini R, Kajstura J, Leri A, Anversa P, Ghezzi P, Salio M, Cerami A, Brines M. Recombinant human erythropoietin protects the myocardium from ischemia-reperfusion injury and promotes beneficial remodeling. Proc Natl Acad Sci USA. 2003;100(8):4802–4806. doi: 10.1073/pnas.0630444100. - DOI - PMC - PubMed
    1. Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F, Nadal-Ginard B, Bodine DM, Leri A, Anversa P. Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci USA. 2001;98(18):10344–10349. doi: 10.1073/pnas.181177898. - DOI - PMC - PubMed

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