Decreased Circulating Endothelial Progenitor Cell Levels and Function in Patients with Nonalcoholic Fatty Liver Disease

ObjectivesNonalcoholic fatty liver disease (NAFLD) is associated with advanced atherosclerosis and a higher risk of cardiovascular disease. Increasing evidence suggests that injured endothelial monolayer is regenerated by circulating bone marrow derived-endothelial progenitor cells (EPCs), and levels of circulating EPCs reflect vascular repair capacity. However, the relation between NAFLD and EPC remains unclear. Here, we tested the hypothesis that patients with nonalcoholic fatty liver disease (NAFLD) might have decreased endothelial progenitor cell (EPC) levels and attenuated EPC function. Methods and ResultsA total of 312 consecutive patients undergoing elective coronary angiography because of suspected coronary artery disease were screened and received examinations of abdominal ultrasonography between July 2009 and November 2010. Finally, 34 patients with an ultrasonographic diagnosis of NAFLD, and 68 age- and sex-matched controls without NAFLD were enrolled. Flow cytometry with quantification of EPC markers (defined as CD34+, CD34+KDR+, and CD34+KDR+CD133+) in peripheral blood samples was used to assess circulating EPC numbers. The adhesive function, and migration, and tube formation capacities of EPCs were also determined in NAFLD patients and controls. Patients with NAFLD had a significantly higher incidence of metabolic syndrome, previous myocardial infarction, hyperuricemia, and higher waist circumference, body mass index, fasting glucose and triglyceride levels. In addition, patients with NAFLD had significantly decreased circulating EPC levels (all P+KDR+ [cells/105 events]) was an independent reverse predictor of NAFLD (Odds ratio: 0.78; 95% confidence interval: 0.69–0.89, P ConclusionsNAFLD patients have decreased circulating EPC numbers and functions than those without NAFLD, which may be one of the mechanisms to explain atherosclerotic disease progression and enhanced cardiovascular risk in patients with NAFLD.研究目的：非酒精性脂肪性肝病（Nonalcoholic fatty liver disease, NAFLD）与进展期动脉粥样硬化及更高的心血管疾病风险密切相关。越来越多的证据表明，循环骨髓源性内皮祖细胞（circulating bone marrow derived-endothelial progenitor cells, EPCs）可修复受损的内皮单层，而循环EPC水平可反映机体的血管修复能力。然而，非酒精性脂肪性肝病与内皮祖细胞之间的关联仍未明确。本研究旨在验证以下假说：非酒精性脂肪性肝病患者的循环内皮祖细胞（endothelial progenitor cell, EPC）水平可能降低，且内皮祖细胞功能受损。 方法与结果：2009年7月至2010年11月期间，共纳入312例因疑似冠状动脉疾病接受择期冠状动脉造影的连续患者，并对其进行腹部超声检查。最终纳入34例经超声诊断为非酒精性脂肪性肝病的患者，以及68例年龄、性别匹配的无NAFLD对照人群。采用流式细胞术对外周血样本中的内皮祖细胞标记物（定义为CD34+、CD34+KDR+及CD34+KDR+CD133+）进行定量分析，以评估循环EPC数量。同时检测两组人群的EPC黏附功能、迁移能力及管形成能力。结果显示，非酒精性脂肪性肝病患者的代谢综合征患病率、既往心肌梗死发生率、高尿酸血症发生率均显著更高，腰围、体重指数、空腹血糖及甘油三酯水平也显著升高。此外，非酒精性脂肪性肝病患者的循环EPC水平显著降低（所有P<0.05）。多因素分析显示，外周血CD34+KDR+细胞数（单位：每10^5个检测事件中的细胞数）是非酒精性脂肪性肝病的独立反向预测因子（比值比：0.78；95%置信区间：0.69~0.89，P<0.001）。 结论：非酒精性脂肪性肝病患者的循环EPC数量及功能均低于无NAFLD的人群，这或许可解释非酒精性脂肪性肝病患者动脉粥样硬化疾病进展及心血管风险升高的部分潜在机制。