Abstract 1387: High Density Lipoprotein Influences Endothelial Progenitor Cell Mobilization, Differentiation, Apoptosis, And Adhesion
Background Bone marrow (BM)-derived endothelial progenitor cells (EPC) enhance endothelial cell repair after focal endothelial cell damage, improve endothelial dysfunction, and are an important cellular risk predictor for cardiovascular mortality and morbidity. High density lipoprotein (HDL) levels inversely correlate with cardiovascular events and seem to have important vasculoprotective effects. Here we postulate that HDL positively influences EPC number and function.
Methods and Results HDL was isolated from young healthy individuals according to standard procedures. EPC were obtained from buffy coats from healthy blood donors. Differentiation of human mononuclear cells into EPC-like DiLDL/lectin-positive cells in vitro after incubation with HDL was significantly enhanced compared to vehicle treated cells. This was due to an inhibition of apoptosis as determined in a flow cytometry-based tunel assay. No differences in proliferation (BrdU incorporation) were observed. Flow chamber experiments revealed a significantly enhanced adhesion process of HDL pre-incubated EPC on human coronary arterial endothelial cells (HCAEC) compared to vehicle treated EPC while HDL treatment of HCAEC significantly prevented adhesion of inflammatory cells. Flow cytometry analyses demonstrated that up-regulation of VLA-4 (CD49d) on HDL pre-incubated EPC may account for the observed effects. Finally, in 250 patients with coronary artery disease we could demonstrate a correlation between the number of circulating EPC and HDL concentrations in peripheral blood.
Conclusion The results indicate that HDL has an important effect on EPC number and function in humans. HDL appears to inhibit EPC apoptosis, enhance the migratory capacity and improve homing of circulating cells by influencing adhesion possibly due to an up-regulation of CD49d. First results indicate that up-regulation of eNOS may account for the beneficial effects of HDL on EPC.