Endothelial progenitor cells as putative targets for angiostatin

Angiostatin, a product of the proteolytic cleavage of plasminogen, possesse s potent antitumor and antiangiogenic properties in vivo. Studies with cult ured endothelial cells suggest that under certain conditions, angiostatin i nhibits the migration and proliferation of these cells or, alternatively, i ncreases their rate of apoptosis. In general, the effects of angiostatin ha ve been considerably less potent in vitro than in vivo. One potential expla nation for this disparity is that the in vivo target of angiostatin is not the mature endothelial cell. Recently, evidence has accumulated to show tha t circulating endothelial progenitor cells (EPCs) contribute to neovascular ization. In this study, we have isolated EPCs from human subjects and demon strated that, in contrast to that of mature endothelial cells, the growth o f EPCs is exquisitely sensitive to angiostatin. These results suggest that angiostatin and related compounds may exert their biological effects by inh ibiting the contribution of EPCs to angiogenesis and not by altering the gr owth of mature endothelial cells.