Publisher： Spandidos Publications
E-ISSN： 1791-3004|11|5|3249-3258
ISSN： 1791-2997
Source： Molecular Medicine Reports, Vol.11, Iss.5, 2015-01, pp. : 3249-3258
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Abstract
Cardiac stem cells (CSCs) can differentiate into cardiac musclelike cells; however, it remains unknown whether CSCs may possess the ability to differentiate into pacemaker cells. The aim of the present study was to determine whether angiotensin II (Ang II) could promote the specialization of CSCs into pacemakerlike cells. Mouse CSCs were treated with Ang II from day 35, after cell sorting. The differentiation potential of the cells was then analyzed by morphological analysis, flow cytometry, reverse transcriptionpolymerase chain reaction, immunohistochemistry and patch clamp analysis. Treatment with Ang II resulted in an increased number of cardiac musclelike cells (32.7±4.8% vs. 21.5±4.8%; P<0.05), and inhibition of smooth musclelike cells (6.2±7.3% vs. 20.5±5.1%; P<0.05). Following treatment with Ang II, increased levels of the cardiac progenitorspecific markers GATA4 and Nkx2.5 were observed in the cells. Furthermore, the transcript levels of pacemaker functionrelated genes, including hyperpolarizationactivated cyclic nucleotidegated (HCN)2, HCN4, Tbox (Tbx)2 and Tbx3, were significantly upregulated. Immunofluorescence analysis confirmed the increased number of pacemakerlike cells. The pacemaker current (If) was recorded in the cells derived from CSCs, treated with Ang II. In conclusion, treatment of CSCs with Ang II during the differentiation process modified cardiacspecific gene expression and resulted in the enhanced formation of pacemakerlike cells.
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