Two types of circulating endothelial progenitor cells in patients receiving long term therapy by HMG-CoA reductase inhibitors.

3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are widely used to decrease cholesterol synthesis and are well established to reduce vascular diseases. Recently, it has been proposed that statins mobilize endothelial progenitor cells from bone marrow during the first four weeks, which could help to prevent vascular diseases. However, in humans there are few data concerning the long term effects of statin treatment on these endothelial progenitor cells. We investigated whether endothelial progenitor cells can be detected and characterized in patients receiving long term statin therapy. Mononuclear cells from patients receiving or not receiving statin therapy were assessed for progenitor cell content by flow cytometry and were cultured in specific conditions to determine the number and the type of progenitors. Our results showed there were significantly more CD34(+), CD34(+)/CD144(+) circulating progenitor cells in the statin(pos) group than in the statin(neg) group. In culture two types of endothelial progenitor cells were detected. Early endothelial progenitor cells gave colonies at day 5 comprising elongated cells whereas late endothelial progenitor cells generated cobblestone-like colonies with strong proliferation capacities. The number of circulating early endothelial progenitor cells was significantly higher in the statin(neg) group, while only late endothelial progenitor cells were detected in the statin(pos) group. Moreover, cells from cobblestones clearly had an endothelial phenotype CD31(+), VEGF-R2(+), CD34(+), CD146(+) in contrast to cells from colonies from early endothelial progenitor cells, which were VEGF-R2(low), CD34(-). These results strongly suggest that long term statin treatment specifically maintains late endothelial progenitor cells in circulation with a CD34(+)/CD144(+) phenotype.