Abstract
The role of erythropoietin (Epo) in myocardial repair after infarction remains inconclusive. We observed high Epo receptor (EPOR) expression in cardiac progenitor cells (CPCs). Therefore, we aimed to characterize these cells and elucidate their contribution to myocardial regeneration on Epo stimulation. High EPOR expression was detected during murine embryonic heart development followed by a marked decrease until adulthood. EPOR-positive cells in the adult heart were identified in a CPC-enriched cell population and showed coexpression of stem, mesenchymal, endothelial, and cardiomyogenic cell markers. We focused on the population coexpressing early (TBX5, NKX2.5) and definitive (myosin heavy chain [MHC], cardiac Troponin T [cTNT]) cardiomyocyte markers. Epo increased their proliferation and thus were designated as Epo-responsive MHC expressing cells (EMCs). In vitro, EMCs proliferated and partially differentiated toward cardiomyocyte-like cells. Repetitive Epo administration in mice with myocardial infarction (cumulative dose 4 IU/g) resulted in an increase in cardiac EMCs and cTNT-positive cells in the infarcted area. This was further accompanied by a significant preservation of cardiac function when compared with control mice. Our study characterized an EPO-responsive MHC-expressing cell population in the adult heart. Repetitive, moderate-dose Epo treatment enhanced the proliferation of EMCs resulting in preservation of post-ischemic cardiac function.
Highlights
Due to the limited regenerative capacity of the heart, cardiovascular diseases remain the main cause of morbidity and mortality in the world (WHO, Fact sheet N317, September 2011)
We focused on the population coexpressing early (TBX5, NKX2.5) and definitive cardiomyocyte markers
Since Epo receptor (EPOR) is predominantly expressed in late stage erythroid progenitors we analyzed its expression during embryonic cardiac development (embryonic day postcoitum (ED) ED7.5, ED8.5, ED9.5, ED10.5, ED13.5, and ED15.5), and postnatal (P) maturation (P1, P3, P6, P10, P13, and 20 weeks old) in NMRI mice
Summary
Due to the limited regenerative capacity of the heart, cardiovascular diseases remain the main cause of morbidity and mortality in the world (WHO, Fact sheet N317, September 2011). Recent evidence suggests that significant myocardial regeneration post-injury in the early neonatal mammalian heart [1], which is lost later mainly due to low cardiomyocyte turnover as shown in the human heart [2]. Two different mechanisms of endogenous cardiomyocyte regeneration have been suggested including proliferating dedifferentiated cardiomyocytes [3] and endogenous progenitor cell differentiation [4]. Neither of these mechanisms is sufficient to replace damaged myocardium in the adult heart. To exploit the dormant regenerative potential of the heart, it is necessary to delineate signaling pathways, which govern the activity of regenerative cell niches within the heart.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
