Physical exercise affects slow cycling cells in the rat heart and reveals a new potential niche area in the atrioventricular junction.

Physical exercise has several beneficial effects on the heart. In other tissues it has been shown to activate endogenous stem cells. There is however a lack of knowledge how exercise affects the distribution of progenitor cells as well as overall cell turnover within the heart. Therefore, proliferating cells were identified using BrdU DNA labeling in a rat exercise model. Slow cycling cells were identified by label retention. BrdU+ nuclei were counted in apex, ventricle and atrioventricular junction (AV junction), as well as in skin tissue where label retaining cells (LRC) have been described previously. After 13 weeks of chasing, the cells with the highest intensity were identified and considered as LRC. Heart tissue showed slower proliferation compared to skin. The highest number of BrdU+ cells was found in the AV junction. Here, a sub region in close proximity to the valvular insertion point was observed, where density of BrdU+ cells was high at all time points. Physical exercise increased proliferation in AV junction at the early stage. Furthermore, the sub region was found to harbor a significant higher number of LRC compared to other regions of the heart in the exercised animals. Progenitor markers MDR1 and Sca-1 were detected in the same area by immunohistochemistry. In conclusions, our data shows that physical exercise affects cell turnover and distribution of LRC in the heart. Furthermore, it reveals a region within the AV junction of the heart that shows features of a stem cell niche.