Human CD34+/KDR+ Cells Are Generated From Circulating CD34+ Cells After Immobilization on Activated Platelets

Objective-The presence of kinase-insert domain-containing receptor (KDR) on circulating CD34(+) cells is assumed to be indicative for the potential of these cells to support vascular maintenance and repair. However, in bone marrow and in granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood, less than 0.5% of CD34(+) cells co-express KDR. Therefore, we studied whether CD34(+)/KDR+ cells are generated in the peripheral circulation. Methods and Results-Using an ex vivo flow model, we show that activated platelets enable CD34(+) cells to home to sites of vascular injury and that upon immobilization, KDR is translocated from an endosomal compartment to the cell-surface within 15 minutes. In patients with diabetes mellitus type 2, the percentage of circulating CD34(+) co-expressing KDR was significantly elevated compared to age-matched controls. When treated with aspirin, the patients showed a 49% reduction in the generation of CD34(+)/KDR+ cells, indicating that the level of circulating CD34(+)/KDR+ cells also relates to in vivo platelet activation. Conclusion-Circulating CD34(+)/KDR+ are not mobilized from bone marrow as a predestined endothelial progenitor cell population but are mostly generated from circulating multipotent CD34(+) cells at sites of vascular injury. Therefore, the number of circulating CD34(+)/KDR+ cells may serve as a marker for vascular injury. (Arterioscler Thromb Vasc Biol. 2011;31:408-415.)