Circulation research
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Circulation research · Oct 2011
Comparative StudyAutologous mesenchymal stem cells mobilize cKit+ and CD133+ bone marrow progenitor cells and improve regional function in hibernating myocardium.
Mesenchymal stem cells (MSCs) improve function after infarction, but their mechanism of action remains unclear, and the importance of reduced scar volume, cardiomyocyte proliferation, and perfusion is uncertain. ⋯ Our results indicate that icMSCs improve function in hibernating myocardium independent of coronary flow or reduced scar volume. This arises from stimulation of myocyte proliferation with increases in cKit+/CD133+ bone marrow progenitor cells and cKit+/CD133- resident stem cells, which increase myocyte number and reduce cellular hypertrophy.
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Circulation research · Oct 2011
Phosphodiesterase 4D regulates baseline sarcoplasmic reticulum Ca2+ release and cardiac contractility, independently of L-type Ca2+ current.
Baseline contractility of mouse hearts is modulated in a phosphatidylinositol 3-kinase-γ-dependent manner by type 4 phosphodiesterases (PDE4), which regulate cAMP levels within microdomains containing the sarcoplasmic reticulum (SR) calcium ATPase type 2a (SERCA2a). ⋯ PDE4D regulates basal cAMP levels in SR microdomains containing SERCA2a-PLN, but not L-type Ca2+ channels or ryanodine receptor. Because whole-cell Ca2+ transient amplitudes are reduced in failing human myocardium, these observations may have therapeutic implications for patients with heart failure.