The adult heart responds to increased workload with physiologic hypertrophy, cardiac stem cell activation, and new myocyte formation.
Bottom Line: In addition, a significant number (∼7%) of smaller newly formed BrdU-positive cardiomyocytes are produced by the exercised animals.Capillary density significantly increased in exercised animals, balancing cardiomyogenesis with neo-angiogenesis. c-kit(pos) eCSCs increased their number and activated state in exercising vs. sedentary animals. c-kit(pos) eCSCs in exercised hearts showed an increased expression of transcription factors, indicative of their commitment to either the cardiomyocyte (Nkx2.5(pos)) or capillary (Ets-1(pos)) lineages.Insulin-like growth factor-1, transforming growth factor-β1, neuregulin-1, bone morphogenetic protein-10, and periostin were significantly up-regulated in cardiomyocytes of exercised vs. sedentary animals.
Affiliation: Stem Cell and Regenerative Biology Unit (BioStem), Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Tom Reilly Building, Byrom Street, Liverpool L3 3AF, UK.Show MeSH
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Mentions: To ascertain whether the different up-regulated myocyte growth factors could be responsible for the activation of the c-kitpos eCSCs in the exercised animals, we tested their effects on c-kitpos eCSC proliferation and differentiation potential in vitro. Dose–response curves were constructed to determine the optimal concentration for each growth factor (Supplementary material online, Figure S6). Addition of IGF-1 and NRG-1 to the culture media enhanced eCSC BrdU incorporation by five- and three-fold, respectively, compared with CTRL (Figure 6A). Importantly, when IGF-1 and NRG-1 were added simultaneously to eCSC cultures, they showed an additive effect, suggesting that they act through separate molecular pathways (Figure 6A). The other growth factors tested did not have any detectable effect on eCSC proliferation. Accordingly, IGF-1 and NRG-1 stimulation was associated with the activation of their respective receptors and physiological molecular signalling targets, Akt and STAT-3, respectively (Figure 6B). The latter have been shown to play a fundamental role in the self-renewal of embryonic and adult stem cells,20,21 generating the hypothesis that these molecular cascades play a similar role in the fate of eCSCs.Figure 6
Affiliation: Stem Cell and Regenerative Biology Unit (BioStem), Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Tom Reilly Building, Byrom Street, Liverpool L3 3AF, UK.