SERUM RANKL/OSTEOPROTEGERIN COMPLEX AND ENDOTHELIAL PROGENITOR CELLS IN CHRONIC HEART FAILURE

A. Berezin, A. Kremzer
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Abstract

The objectiveof this study was to assess an interrelationship serum RANKL/OPG complex with counts of circulating pro-angiogenic endothelial progenitor cells (EPCs) labeled as CD14+CD309+, and CD14+CD309+Tie2+ in patients with ischemic chronic heart failure (CHF).Methods: The study retrospectively evolved 153 patients (86 males) aged 48 to 62 years with exiting proven stable coronary artery disease (CAD). Systolic or diastolic CHF was defined among 109 (71.2%) patients. Twenty five 25 individuals were included in the control group. Circulating RANKL (sRANKL) and OPG were measured by high-sensitive ELISA kit at baseline. EPC populations were labeled by flow cytofluorimetry per High-Definition Fluorescence Activated Cell Sorter methodology.Results: Numerous of EPCs with phenotypes of CD14+CD309+ and CD14+CD309+Tie2+ were significantly lower in CAD patients when compared with healthy subjects. The trend to significant decrease of EPC numerous depending presence of CHF was found. The sRANKLlevel, OPG level, and sRANKL / OPG ratio were significantly higher in CHF subjects as compared to those without CHF (P=0.001). On multivariate analysis, CHF, sRANKL/OPG ratio, OPG, and NT-pro-BNP remained as independent predictors of decreased EPCs with phenotypes of CD14+CD309+ and CD14+CD309+Tie2+. When sRANKL/OPG ratio was added to the standard predictive model (CHF) improved relative integrated discrimination indices by 12.5% for CD14+CD309+ depletion, as well as by 17.3% for CD14+CD309+Tie2+depletion were found. Conclusion: We found that sRANKL/OPG ratio remained statistically significant predictor for depletion of pro-angiogenicEPCsin CAD patients.
血清兰克尔/骨保护素复合物和内皮祖细胞在慢性心力衰竭中的作用
本研究的目的是评估缺血性慢性心力衰竭(CHF)患者血清RANKL/OPG复合物与循环中标记为CD14+CD309+和CD14+CD309+Tie2+的促血管生成内皮祖细胞(EPCs)计数的相互关系。方法:回顾性分析153例(86例男性)患者,年龄48 ~ 62岁,已证实为稳定型冠心病(CAD)。109例(71.2%)患者诊断为收缩期或舒张期CHF。25人被纳入对照组。基线时采用高灵敏ELISA试剂盒检测循环RANKL (sRANKL)和OPG。流式细胞荧光法根据高清荧光活化细胞分选法对EPC群体进行标记。结果:与健康受试者相比,冠心病患者中CD14+CD309+和CD14+CD309+Tie2+表型的EPCs数量明显减少。发现随着CHF的存在,EPC数有显著降低的趋势。与非CHF组相比,CHF组的sRANKL水平、OPG水平和sRANKL / OPG比值显著升高(P=0.001)。在多变量分析中,CHF、sRANKL/OPG比值、OPG和NT-pro-BNP仍然是CD14+CD309+和CD14+CD309+Tie2+表型的EPCs减少的独立预测因子。当标准预测模型(CHF)中加入sRANKL/OPG比值时,CD14+CD309+缺失的相对综合判别指数提高了12.5%,CD14+CD309+Tie2+缺失的相对综合判别指数提高了17.3%。结论:我们发现sRANKL/OPG比值仍然是CAD患者促血管生成epcsin消耗的有统计学意义的预测因子。
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