Ageing and endothelial progenitor cellrelease of proangiogenic cytokines

SIR—Circulating endothelial progenitor cells (EPCs) are widely recognised to contribute to the reparative process of the vascular endothelium and participate in angiogenesis [1]. Although declines in the circulating population of EPCs are associated with poor cardiovascular disease prognosis and are predictive of future adverse cardiovascular events [2], transplantation of ex vivo expanded EPCs into the coronary artery can rescue ischaemic tissue and significantly improve coronary function in patients with myocardial infarction [3]. The angiogenic potential of these cells can be explained, in part, through their ability to home to local sites of ischaemia and vascular damage and secrete potent proangiogenic factors, such as cytokines, chemokines and growth factors, which are integral in promoting new blood vessel formation and repair. For example, both vascular endothelial growth factor (VEGF) [4] and granulocyte-colony stimulating factor (G-CSF) [5] stimulate recruitment and migration of EPCs from the bone marrow, inhibit apoptosis and support the angiogenic capacity of mature endothelial cells [6, 7]. In addition, interleukin (IL)-8, a proangiogenic cytokine, has been shown to attract EPCs to infarcted tissue and enhance the effect of G-CSF to mobilise progenitor cells from the bone marrow [8–10]. In older adults, endothelial injury and compromised EPC-mediated vascular repair are thought to contribute to atherosclerosis [11]. We have previously reported that EPC colony-forming capacity, migration and telomere length decline with ageing [12, 13]. In the present study, we tested the hypothesis that the capacity of circulating EPCs to release proangiogenic cytokines declines with age in healthy adults.