BACKGROUND AND OBJECTIVES: The increased risk of cardiovascular disease in patients with chronic renal failure (CRF) has been explained by accelerated atherosclerosis and impaired angiogenesis, where endothelial progenitor cells (EPC) may play key roles. It was hypothesized that : "an altered EPC biology may contribute to the pathophysiology of CRF". SUBJECTS AND METHODS: EPC were isolated from CRF patients on maintenance hemodialysis (n=44) and from a normal control group (n=30). After morphological and immunological characterization, the number and in vitro angiogenic function of the EPC were evaluated. RESULTS: CRF patients showed markedly decreased numbers of EPC (44.6%) and colonies (75.3%) compared to the controls (p<0.001). These findings were corroborated by a 30.5% decrease in the migratory function in response to vascular endothelial growth factor (VEGF)(p=0.040) and by a 48.8% decrease in EPC incorporation into human umbilical vein endothelial cells (HUVEC)(p<0.001). In addition, The Framingham's risk factor scores of both the CRF (r=-0.461, p=0.010) and normal groups (r=-0.367, p=0.016) were significantly correlated with the numbers of EPC. Indeed, under the same burden of risk factors the number of circulating EPC was significantly lower in CRF patients than in the normal group (p<0.001). A significant correlation was also observed between the dialysis dose (Kt/V) and EPC incorporation into the HUVEC (r=0.427, p=0.004). CONCLUSION: The EPC biology, which is critical for neovascularization and the maintenance of vascular function, was altered in CRF. Our data strongly suggest that dysfunction of circulating EPC has a role in the progression of cardiovascular disease in patients with CRF.
Atherosclerosis ; Biology ; Cardiovascular Diseases ; Coronary Artery Disease ; Dialysis ; Endothelial Cells ; Human Umbilical Vein Endothelial Cells ; Humans ; Kidney Failure, Chronic* ; Renal Dialysis ; Risk Factors ; Stem Cells* ; Vascular Endothelial Growth Factor A