Exercise-induced physiological hypertrophy initiates activation of cardiac progenitor cells

Objective: Physiological hypertrophy is featured by the hypertrophy of pre-existing cardiomyocytes and the formation of new cardiomyocytes. C-kit positive cardiac progenitor cells increased their numbers in exercise-induced physiological hypertrophy. However, the participation of Sca-1 positive cells in the physiological adaptation of the heart to exercise training is unclear. Methods: Physiological hypertrophy was induced by swimming and the mRNA levels of GATA binding protein 4 (GATA4), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), endogenous hepatocyte growth factor (HGF), and insulin like growth factor-1 (IGF-1) from the whole heart were determined by real-time polymerase chain reactions (RT-PCRs) analysis. Immunofluorescent staining was used to compare the number of C-kit and Sca-1 positive cardiac progenitor cells. In addition, mRNA levels of C-kit and Sca-1 in left ventricle (LV), right ventricle (RV), and outflow tract (OFT) were determined in mice swimming for 7, 14, and 21 days by RT-PCRs. Results: The ratio of heart weight (HW) to body weight and HW to tibia length and the mRNA level of GATA4 were increased while mRNA levels of ANP and BNP remained unchanged. C-kit and Sca-1 positive cardiac progenitor cells were activated by swimming training. An increased endogenous production of HGF and IGF was observed at least at the mRNA level. Swimming induced a significant up-regulation of C-kit in LV of mice swimming for 1, 2 and 3 weeks and in RV of mice swimming for 3 weeks. Sca-1 positive cardiac progenitor cells were increased in LV and OFT in mice swimming for 3 weeks. Conclusion: This study presents that swimming-induced physiological hypertrophy initiates activation of cardiac progenitor cells.