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- W2083245162 abstract "Cardiac progenitor cells (CPC) are a progenitor cell population within the myocardium and are activated after a myocardial infarction (MI) to proliferate, migrate to the infarct region, and participate in cardiac regeneration. Enhancement of the CPC response has been suggested as a potential therapeutic approach to diminish cardiac injury after a MI. Ionic currents, Ca2+ flux, and β-adrenergic signaling have been proposed to promote CPC activation though the mechanisms are unclear. We therefore investigated the cellular mechanisms (Ca2+ signaling, ion currents) that could promote the proliferation and regeneration potential of CPC. Murine CPC were isolated from adult hearts and selected by c-kit magnetic sorting. Flow cytometry analysis confirmed a high purity of the c-kit+ CPC. Cardiac myocyte differentiation potential of the CPC was evaluated by treatment of 10 nM dexamethasone for one week. After treatment, 85.9 ± 6.0% of the CPC expressed α-sarcomeric actinin. We identified expression of β-adrenergic receptors 1, 2 and 3 on CPC by immunostaining. Intracellular Ca2+ levels in CPC were evaluated by Fura-2 AM. ATP (10 μM) induced a rapid rise in CPC Ca2+ levels (98 ± 2% of CPC responding) followed by Ca2+ oscillations. Isoprenaline (10 nM) increased Ca2+ levels in 24.2 ± 10.7% of CPC. Caffeine, endothelin 1, and phenylephrine did not alter intracellular Ca2+ levels of CPC. Patch clamp studies revealed the lack of functional inward Na+ or Ca2+ currents but the presence of functional slowly-inactivating outward voltage-gated K+. CPC have functional ATP specific P2-purinoreceptors and β-adrenergic receptors but do not express functional ryanodine, endothelin, or α-adrenergic receptors. Further experiments will determine the functional relevance of these signaling mechanisms in CPC proliferation and differentiation. Acquisition of this knowledge could help define conditions to augment cardiac repair after MI." @default.
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- W2083245162 date "2014-04-01" @default.
- W2083245162 modified "2023-09-28" @default.
- W2083245162 title "0334: Cellular mechanisms to enhance the regeneration potential of cardiac progenitor cells" @default.
- W2083245162 doi "https://doi.org/10.1016/s1878-6480(14)71318-7" @default.
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