Abstract 3984: Liberation of Early Tissue-committed Stem Cells From the Bone Marrow by Exercise Training: Impact on Left Ventricular Function in Rats With Chronic Myocardial Infarction
Tissue lineage-committed stem cells are transiently released from the bone marrow after myocardial infarction. Exercise training (ET) is known to augment the number of stem cells persistently, at least in healthy individuals. In this study we aimed to determine, whether ET -that is a powerful therapeutic intervention in secondary prevention - induces the release of tissue-committed stem cells in chronic myocardial infarction.
Methods: Male Wistar Kyoto rats underwent LAD ligation (MI) or sham operation (Sham). After 3 weeks, animals of both groups were subjected to an inactive lifestyle (Sham-C n=12; MI-C, n=12) or ET (Sham-T, n=12; MI-T, n=12). Animals in the training groups were exercising on a treadmill 1 hour daily for a period of 4 weeks. CD34+ stem cells were quantified by FACS. In circulating cells, expression of vimentin, von Willebrand factor (vWF), and myogenin as a marker of fibroblast, endothelial, and skeletal muscle lineage-commitment was determined by RT-PCR. Hemodynamics were measured by echocardiography and conductance catheter.
Results: The CD34+ cell count did not differ between Sham-C (421±43 cells) and MI-C (388±41 cells). In contrast, the expression of vimentin was elevated 3.2fold in circulating cells in MI-C (p<0.05). ET increased the number of CD34+ cells in sham-operated animals (Sham-T: 622±63 cells, p<0.05 vs. Sham-C), but in particular in rats with chronic MI (MI-T: 1057±89 cells, p<0.05 vs. MI-C und Sham-T). In rats with chronic MI exercise training enhanced the expression of vWF and myogenin 3.8fold and 6.6fold (p<0.05 vs. all other groups), respectively, indicating an endothelial- and skeletal muscle lineage-commitment of those cells. Moreover, ET normalized the mRNA abundance of vimentin in circulating stem cells in these animals (p<0.05 vs. all other groups). The ET-induced release of tissue-committed stem cells was associated with an augmentation in left ventricular performance in chronic MI.
Conclusion: In chronic MI, ET increases the number of CD34+ stem cells and promotes a tissue lineage-commitment of those cells. The ongoing tissue analysis will reveal, whether the improvement in left ventricular function in exercise-trained animals with chronic MI is the result of stem cell-mediated cardiac repair.