Homocysteine accelerates senescence and reduces proliferation of endothelial progenitor cells

Our previous studies showed that homocysteine (Hey) reduces endothelial progenitor cell (EPC) numbers and impairs functional activity. However, the mechanisms by which Hey reduces EPCs numbers and activity remain to be determined. Recent studies have demonstrated that reduced EPCs numbers and activity was associated with EPCs senescence which involved telomerase activity. Therefore, we investigated whether Hey accelerates the onset of EPCs senescence through telomerase inactivation, leading to cellular dysfunction. EPCs were isolated from peripheral blood and characterized. After ex vivo cultivation, EPCs became senescent as determined by acidic P-galactosidase staining. Hey dose-dependently accelerated the onset of EPCs senescence in culture. Moreover, Hey decreased proliferation of EPCs as assessed by BrdU incorporation assay and colony-fanning capacity. To get further insights into the underlying mechanisms of these effects induced by Hey, we measured telomerase activity and determined the phosphorylation of Akt by using western blot. Hey significantly diminished telomerase activity and Akt phosphorylation. Taken together, the results of the present study demonstrated that Hey accelerated the onset of EPCs senescence, leading to cellular dysfunction. The effect of Hey might be dependent on telomerase inactivation, and Akt dephosphorylation also appeared to play a major role. In addition, atorvastatin had a preventative effect against Hcy-induced EPCs senescence. (c) 2006 Elsevier Ltd. All fights reserved.