In cardiac hypertrophy associated with pathological

In cardiac hypertrophy associated with pathological processes, it has been shown that CSCs participate in the reparative processes (Ellison et al., 2013; Leri et al., 2005); however, extensive damage cannot be completely reversed, indicating that the regenerative potential of these stem ACA cost during a damage challenge is limited (Chan et al., 2009; Hatzistergos et al., 2010B; Bailey et al., 2009). For the physiological cardiac hypertrophy observed in exercise training (Waring et al., 2014; Xiao et al., 2014b), pregnancy (Xiao et al., 2014a) or postnatal growth (Mann and Rosenzweig, 2012), little is known about the role of resident CSCs. Waring et al. (2014) have demonstrated that c-Kit+ CSCs play an active role during physiological cardiac hypertrophy in mice specifically for exercise training. Whether the CMSCs are involved is not yet known. Because of the evidence supporting the existence of circulating stem cells capable of differentiating into cardiogenic cells (Beltrami et al., 2003; Quaini et al., 2002), it would also be worthwhile to investigate whether physical exercise training creates an attractive stimulus for noncardiac undifferentiated cells. Therefore, the aim of the present study was to quantify the number of three different types of resident multipotent CSCs (c-Kit+Lin−, Sca-1+Lin− and CMSCs) in a mouse model of physiologically hypertrophied hearts. Another aim was to determine whether extracardiac stem cells are recruited to the heart during physiological cardiac hypertrophy using a parabiotic eGFP transgenic/wild-type mouse model.
Methods
Results
Discussion To further support our morphological data showing physiological cardiac hypertrophy, the electrocardiographic study showed that, as a consequence of the cardiac structural changes resulting from the work overload, the swimming exercise training was also associated with the expected electrocardiographical changes, mainly the sinus bradycardia, which can be caused by autonomic nervous system adjustments (Corrado et al., 2009) or changes in ion channel expression in the heart after the cardiac overload induced by exercise training. QT interval, which represents most closely ventricular systole by contemplate the ventricular electrical depolarization and repolarization period, proved to be extended in the trained animals. However, when the QT interval was corrected by the RR interval, the duration of the ventricular electrical activity did not differ between groups, a finding that is physiologically expected as an indicator of normal cardiac electrical activity. In contrast, pathological cardiac hypertrophy, such the consequent to Chagas disease, occurs with a prolonged corrected QT interval (de Cuba et al., 2014), indicating a prolongation of the cardiac electrical action potential. Concerning the CSCs in the physiologically hypertrophied hearts, the findings regarding the numerical increase in c-Kit+Lin− CSCs match with those found by Waring et al. (2014), who used running exercise training. During exercise training, the apoptosis and/or necrosis rate in physiologically hypertrophied hearts are in fact normal (Jin et al., 2000) or even reduced (Siu et al., 2004); thus, we could hypothesize that the increase in c-Kit+Lin− CSCs could be due to an increase in the rate of proliferation of these cells, as suggested by Waring et al. (2014), or due to a reduced apoptosis/necrosis rate. Unlike c-Kit+Lin− cells, the number of Sca-1+Lin− CSCs did not increase in the physiologically hypertrophied heart after exercise training. This finding was different from those presented by Xiao et al. (2014b). Such inconsistence may reflect the different methods and/or different tissue samples used. While Xiao et al. (2014b) investigated the Sca-1+ cells in sections of the apex of the heart by means of immunofluorescence microscopy (Xiao et al., 2014b), in the present study the measurements were done considering the absolute number of Sca-1+Lin− cells obtained from a myocyte-depleted cell fraction of the total heart. Furthermore, the coexpression of any hematopoietic cell lineage marker was excluded from our cell samples by using an anti-lineage antibodies cocktail. In our study, the inability to increase the number of Sca-1+Lin− cells in the heart after exercise training remains to be elucidated.