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. CONCLUSIONS: 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.
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. CONCLUSIONS: 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.
Authors: Anastasia D Egorova; Marco C DeRuiter; Hetty C de Boer; Simone van de Pas; Adriana C Gittenberger-de Groot; Anton J van Zonneveld; Robert E Poelmann; Beerend P Hierck Journal: In Vitro Cell Dev Biol Anim Date: 2011-11-20 Impact factor: 2.416
Authors: G Mandraffino; E Imbalzano; M A Sardo; A D'Ascola; F Mamone; A Lo Gullo; A Alibrandi; S Loddo; E Mormina; A David; A Saitta Journal: J Hum Hypertens Date: 2014-02-20 Impact factor: 3.012
Authors: Alberto Lo Gullo; Giuseppe Mandraffino; Gianluca Bagnato; Caterina Oriana Aragona; Egidio Imbalzano; Angela D'Ascola; Francesco Rotondo; Antonella Cinquegrani; Enricomaria Mormina; Carlo Saitta; Antonio Giovanni Versace; Maria Adriana Sardo; Renato Lo Gullo; Saverio Loddo; Antonino Saitta Journal: PLoS One Date: 2015-08-04 Impact factor: 3.240