Effects of adrenomedullin on the cell numbers and apoptosis of endothelial progenitor cells.

PURPOSE To investigate the effect of adrenomedullin on the cell numbers and apoptosis of endothelial progenitor cells (EPCs). METHODS Mononuclear cells were isolated from peripheral blood by Ficoll density gradient centrifugation. The cells were stimulated with adrenomedullin, before and after the treatment of adrenomedullin-receptor antagonist, adrenomedullin 22-52, or a PI3K inhibitor LY294002. RESULTS Adrenomedullin dose-dependently increased the number of EPCs (P < 0.05). Adrenomedullin also significantly decreased apoptosis rate of EPCs in a concentration-dependent manner (P < 0.05). In the isolated human mononuclear cells pretreated with adrenomedullin 22-52 or LY294002, adrenomedullin failed to increase the number of EPCs or to reduce the level of apoptosis. CONCLUSIONS Adrenomedullin increases the number of EPCs and decreases their apoptosis. These actions are likely mediated by PI3K signaling pathways. The clinical importance of these favourable effects on EPCs remains to be determined.