Leptin receptor and functional effects of leptin in human endothelial progenitor cells.

Circulating endothelial progenitor cells (EPCs) may be involved in the maintenance of vascular homeostasis and their impairment may be conducive to vascular disease. We studied the role of an adipocyte-derived hormone, leptin, in the regulation of human EPC function. EPCs were grown from human circulating mononuclear cells. The presence of the leptin receptor and the functional effects of leptin in EPCs were investigated. EPCs stained positive for endothelial cell markers (Flk-1 and Tie-2 receptors) and the hematopoietic CD34 marker. The presence of the long form of the leptin receptor in EPCs was confirmed by Western blotting and with immunofluorescence. Leptin, at a physiological concentration of 10 ng/ml, significantly increased tube formation from 2.1+/-2.2 to 12.4+/-4.9 tubes/25 mm2. At a higher concentration of 100 ng/ml of leptin, tube formation was reduced compared to the lower concentration. This higher concentration of leptin also inhibited EPC migration, decreasing it from 0.45+/-0.14 to 0.28+/-0.12 mm/48 h. Leptin did not have any effect on EPC proliferation. In summary, the leptin receptor is present in human EPCs and leptin may affect EPC function, both in physiological and in hyperleptinemic conditions. These findings are relevant to leptin-mediated regulation of vasculogenesis in humans, and the association between hyperleptinemia and obesity with cardiovascular disease.