Stem cells, Myocardial adaptation and Physical exercise
The discovery of resident endogenous cardiac stem-progenitor cells (eCSCs) in the adult heart has contributed greatly to a new view of cardiac biology. A variety of markers have been proposed to identify eCSCs in different species. Despite the significant regenerative potential of the c-kitposeCSCs, the role of c-kitposeCSCs in cardiac physiological remodelling induced by exercise training remains to be determined. Recent data have advanced the hypothesis that the ‘physiological hypertrophy’ produced by exercise training, at odds with pathological hypertrophy, is accompanied also by adult cardiomyocyte division in vivo. It was shown that treadmill exercise training, which can be intensity, controlled according to individual VO2 max, stimulates the activation of c-kitposeCSCs and induces new cardiomyocyte and capillary formation, thereby contributing to the physiological remodelling of the heart. In addition it was also shown that the physiological adaptation of the adult heart to an increased cardiac workload, induced by the exercise programme, has three main components: (i) physiological hypertrophy of the existing myocytes, accompanied by their increased production of specific growth factors which through auto- and paracrine loops foster their own survival and hypertrophy as well as activating the c-kitpos eCSCs; (ii) the activation of c-kitpos eCSCs, which increase in number and undergo a process of cell specification and differentiation towards the myocyte and vascular lineages; and (iii) the accumulation of new myocardial cells, namely new myocytes and microvasculature.
Exercise exerts its beneficial effects not just through reducing the burden of classical cardiovascular risk factors, but also directly affecting the cellular and molecular structure and function of the heart, and data showed that exercise up-regulated factors differentially govern c-kitposeCSC fate in vitro, pointing to a similar effect in vivo. Thus, eCSCs from the adult heart exhibit a response to many growth factors that recapitulates, at least in part, embryonic cardiac progenitor activation and lineage commitment. It has been reported that down-regulation of the transcription factor C/EBP b in swim exercise-trained mice appears to be a central mediator of physiological myocyte hypertrophy and proliferation, which accounts for 6% of new myocyte formation [10].