Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
Nephrol Dial Transplant. 2010 Jun;25(6):1875-82. doi: 10.1093/ndt/gfp749. Epub 2010 Jan 18.
Endothelial dysfunction contributes to accelerated atherosclerosis in chronic kidney disease (CKD). Bone marrow-derived endothelial progenitor cells (EPC) constitute an endogenous vascular repair system protecting against atherosclerosis. Smooth muscle progenitor cells (SPC) may stimulate atherosclerosis development. We hypothesized that an imbalance in EPC and SPC occurs in CKD, which may contribute to the increased cardiovascular disease (CVD) risk.
EPC and SPC outgrowth from mononuclear cells (MNC), EPC migratory function and circulating CD34(+)KDR(+)-EPC were measured in 49 patients with varying degrees of CKD on regular therapy and 33 healthy volunteers. Renal function, CKD cause, CVD history and endothelial dysfunction parameters were determined as factors of influence on progenitor cells.
Patients had reduced EPC outgrowth compared to controls [9 (2-22) vs 12 (1-38) cells/10(3) MNC, P = 0.026], independent of CKD cause and degree, whereas SPC outgrowth levels were higher in patients with more impaired kidney function (r = -0.397, P = 0.008). Patients had lower CD34(+)KDR(+)-EPC compared to controls [9 (0-52) vs 19 (4-110) cells/10(5) granulocytes, P = 0.004]. CVD history and increased endothelial dysfunction markers were related to lower EPC levels. Progenitor cell outgrowth was shifted towards SPC with progression of endothelial damage. Reduction in EPC could not be attributed to decreases in progenitor cell-mobilizing factors SDF-1 alpha and VEGF as levels increased with progressive kidney and endothelial dysfunction, while EPC remained low.
Our data suggest that, already in mild CKD, EPC-mediated endogenous vascular regeneration is impaired, while SPC levels increase with declining kidney function.
内皮功能障碍导致慢性肾脏病（CKD）患者动脉粥样硬化加速。骨髓来源的内皮祖细胞（EPC）构成了一种内源性血管修复系统，可预防动脉粥样硬化。平滑肌祖细胞（SPC）可能会刺激动脉粥样硬化的发展。我们假设，CKD 患者中存在 EPC 和 SPC 的失衡，这可能导致心血管疾病（CVD）风险增加。
在常规治疗的 49 名不同程度 CKD 患者和 33 名健康志愿者中，测量单核细胞（MNC）中 EPC 和 SPC 的生长、EPC 迁移功能和循环 CD34(+)KDR(+)-EPC。确定肾功能、CKD 病因、CVD 病史和内皮功能障碍参数作为影响祖细胞的因素。
与对照组相比，患者的 EPC 生长减少[9（2-22）vs 12（1-38）个细胞/10(3)MNC，P = 0.026]，与 CKD 病因和程度无关，而肾功能受损越严重的患者 SPC 生长水平越高（r = -0.397，P = 0.008）。与对照组相比，患者的 CD34(+)KDR(+)-EPC 水平较低[9（0-52）vs 19（4-110）个细胞/10(5)粒细胞，P = 0.004]。CVD 病史和内皮功能障碍标志物升高与 EPC 水平降低相关。随着内皮损伤的进展，祖细胞的生长向 SPC 转移。EPC 的减少不能归因于祖细胞动员因子 SDF-1 alpha 和 VEGF 的减少，因为这些因子随着肾功能和内皮功能障碍的进展而增加，而 EPC 仍然较低。
我们的数据表明，在轻度 CKD 中，EPC 介导的内源性血管再生已经受损，而 SPC 水平随着肾功能的下降而升高。
