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进行性慢性肾病患者的内皮祖细胞功能障碍

Endothelial progenitor cell dysfunction in patients with progressive chronic kidney disease.

作者信息

Krenning Guido, Dankers Patricia Y W, Drouven Johannes W, Waanders Femke, Franssen Casper F M, van Luyn Marja J A, Harmsen Martin C, Popa Eliane R

机构信息

Stem Cell and Tissue Engineering Research Group, Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (EA11 NL-9713GZ, Groningen, The Netherlands.

出版信息

Am J Physiol Renal Physiol. 2009 Jun;296(6):F1314-22. doi: 10.1152/ajprenal.90755.2008. Epub 2009 Apr 1.

Abstract

Endothelial progenitor cells (EPC) contribute to repair and maintenance of the vascular system, but in patients with chronic kidney disease (CKD), the number and function of EPC may be affected by kidney dysfunction. We assessed numbers and the angiogenic function of EPC from patients with CKD in relation to disease progression. In a cross-sectional, prospective study, 50 patients with varying degrees of CKD, including 20 patients undergoing dialysis and 10 healthy controls, were included. Mononuclear cells were isolated, and circulating EPC were quantified by flow cytometry based on expression of CD14 and CD34. EPC were cultured on fibronectin-coated supramolecular films of oligocaprolactone under angiogenic conditions to determine their angiogenic capacity and future use in regenerative medicine. CKD patients had normal numbers of circulating CD14+ EPC but reduced numbers of circulating CD34+ EPC. Furthermore, EPC from patients with CKD displayed functional impairments, i.e., hampered adherence, reduced endothelial outgrowth potential, and reduced antithrombogenic function. These impairments were already observed at stage 1 CKD and became more apparent when CKD progressed. Dialysis treatment only partially ameliorated EPC impairments in patients with CKD. In conclusion, EPC number and function decrease with advancing CKD, which may hamper physiological vascular repair and can add to the increased risk for cardiovascular diseases observed in CKD patients.

摘要

内皮祖细胞(EPC)有助于血管系统的修复和维持,但在慢性肾脏病(CKD)患者中,EPC的数量和功能可能会受到肾功能不全的影响。我们评估了CKD患者EPC的数量及其血管生成功能与疾病进展的关系。在一项横断面前瞻性研究中,纳入了50例不同程度的CKD患者,包括20例接受透析的患者和10例健康对照者。分离单核细胞,并基于CD14和CD34的表达通过流式细胞术对循环EPC进行定量。将EPC在血管生成条件下培养于纤连蛋白包被的聚己内酯超分子膜上,以确定其血管生成能力以及在再生医学中的未来应用。CKD患者循环CD14 + EPC数量正常,但循环CD34 + EPC数量减少。此外,CKD患者的EPC表现出功能受损,即黏附受阻、内皮细胞生长潜能降低和抗血栓形成功能降低。这些损害在CKD 1期就已观察到,并且在CKD进展时变得更加明显。透析治疗仅部分改善了CKD患者的EPC损害。总之,随着CKD的进展,EPC数量和功能下降,这可能会阻碍生理性血管修复,并增加CKD患者心血管疾病的风险。

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