血液循环中微小RNA-140-3p和Toll样受体4表达与冠心病患者经皮冠状动脉介入术后支架内再狭窄的关系研究

Relations between the Expression of MicroRNA-140-3p and TLR4 in Blood Circulation and In-stent Restenosis after Percutaneous Coronary Intervention in Patients with Coronary Heart Disease

背景支架内再狭窄是影响经皮冠状动脉介入术(PCI)患者远期预后的主要不良事件之一。Toll样受体(TLR)介导的炎性反应和血管内皮损伤在PCI后支架内再狭窄机制中发挥着重要作用,故围绕该机制筛选生物标志物对PCI后患者管理具有重要意义。目的分析血液循环中微小RNA-140-3p(miR-140-3p)和TLR4表达与冠心病患者PCI后支架内再狭窄的关系。方法选取上海市杨浦区市东医院2016年7月—2017年12月收治的行PCI的285例冠心病患者作为病例组,根据有无发生支架内再狭窄将冠心病患者分为再狭窄亚组(n=44)和无再狭窄亚组(n=241)。另选取同期在上海市杨浦区市东医院进行健康体检的300例中老年(45~75岁)健康志愿者作为对照组。比较病例组与对照组miR-140-3p、TLR4相对表达量,再狭窄亚组与无再狭窄亚组患者人口学特征、合并症、生活习惯、实验室检查指标、影像学资料及PCI情况;miR-140-3p、TLR4相对表达量与冠心病患者PCI后支架内再狭窄的关系分析采用多因素Logistic回归分析及ROC曲线。结果病例组患者miR-140-3p相对表达量低于对照组,TLR4相对表达量高于对照组(P<0.05)。再狭窄亚组患者糖尿病发生率、空腹血糖、超敏C反应蛋白(hs-CRP)、降钙素原(PCT)、TLR4相对表达量、冠状动脉狭窄率高于无再狭窄亚组,miR-140-3p相对表达量及左心室射血分数(LVEF)低于无再狭窄亚组,支架内径小于无再狭窄亚组(P<0.05)。多因素Logistic回归分析结果显示,糖尿病、PCT及TLR4相对表达量是冠心病患者PCI后支架内再狭窄的危险因素,而miR-140-3p相对表达量、LVEF及支架内径是冠心病患者PCI后支架内再狭窄的保护因素(P<0.05)。ROC曲线分析结果显示,miR-140-3p、TLR4相对表达量预测冠心病患者PCI后支架内再狭窄的曲线下面积(AUC)分别为0.866、0.798,与PCT的0.862比较,差异无统计学意义(P>0.05),但高于LVEF的0.531(P<0.05)。结论血液循环中miR-140-3p和TLR4表达是冠心病患者PCI后支架内再狭窄的影响因素,且二者对冠心病患者PCI后支架内再狭窄的预测价值较高,可作为预测冠心病患者PCI后支架内再狭窄的生物标志物。

Background In-stent restenosis is one of the major adverse events affecting the long-term prognosis of patients after percutaneous coronary intervention(PCI).Inflammatory response and vascular endothelial injury mediated by Toll-like receptor(TLR)play an important role in the mechanism of in-stent restenosis after PCI,therefore,screening biomarkers around this mechanism is of great significance to the management of patients after PCI.Objective To analyze the relationship between the expression of microRNA-140-3p(miR-140-3p)and TLR4 in blood circulation and in-stent restenosis after PCI in patients with coronary heart disease.Methods A total of 285 patients with coronary heart disease who underwent PCI in Shidong Hospital of Yangpu District,Shanghai from July 2016 to December 2017 were selected as the case group,and they were divided into restenosis subgroup(n=44)and no-restenosis subgroup(n=241)according to the occurrence of in-stent restenosis.Meanwhile 300 cases middle-aged and elderly(45-75 years old)healthy volunteers who had physical examination in East City Hospital of Yangpu District,Shanghai were selected as control group.The relative expression levels of miR-140-3p and TLR4 were compared between the case group and the control group.The demographic characteristics,complications,living habits,laboratory examination indexes,imaging data and PCI circumstances were compared between restenosis subgroup and no-restenosis subgroup.The relationship between the relative expression levels of miR-140-3p and TLR4 and in-stent restenosis after PCI in patients with coronary heart disease was analyzed by multivariate Logistic regression analysis and ROC curve.Results The relative expression level of miR-140-3p in the case group was lower than that in the control group,while the relative expression level of TLR4 was higher than that in the control group(P<0.05).The incidence of diabetes mellitus,fasting blood glucose,high sensitivity C-reactive protein(hs-CRP),procalcitonin(PCT),relative expression level of TLR4,coronary artery stenosis rate in the restenosis subgroup were higher than those in the no-restenosis subgroup,relative expression level of miR-140-3p and left ventricular ejection fraction(LVEF)were higher than those in the no-restenosis subgroup,while the stent diameter was smaller than that in the no-restenosis subgroup(P<0.05).Multivariate Logistic regression analysis showed that,diabetes mellitus,PCT,relative expression level of TLR4 were the risk factors of instent restenosis after PCI in patients with coronary heart disease,while the relative expression level of miR-140-3p,LVEF and stent diameter were the protective factors of in-stent restenosis after PCI in patients with coronary heart disease(P<0.05).ROC curve analysis showed that,the AUC of relative expression levels of miR-140-3p and TLR4 in predicting in-stent restenosis after PCI in patients with coronary heart disease was 0.866 and 0.798,respectively,which was similar to the PCT of 0.862(P>0.05),but was higher than that of LVEF of 0.531(P<0.05).Conclusion The expression of miR-140-3p and TLR4 in blood circulation are the influencing factors of in-stent restenosis after PCI in patients with coronary heart disease,and they have relatively high predictive value on in-stent restenosis after PCI in patients with coronary heart disease,which can be biomarkers for predicting in-stent restenosis after PCI in patients with coronary heart disease.