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中间单核细胞会导致糖尿病STEMI患者的心肌重塑增强。

Intermediate monocytes lead to enhanced myocardial remodelling in STEMI patients with diabetes.

作者信息

Lu Wenbin, Zhang Ziwei, Fu Cong, Ma Genshan

机构信息

Department of Cardiology, ZhongDa Hospital Affiliated to Southeast University China; Division of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University, Nanjing, China.

出版信息

Int Heart J. 2015;56(1):22-8. doi: 10.1536/ihj.14-174. Epub 2014 Dec 11.

Abstract

This study aimed to evaluate the potential associations of intermediate monocytes (CD14(++)CD16(+)) with myocardial remodelling in ST segment elevation myocardial infarction (STEMI) patients with diabetes.A total of 67 STEMI patients with diabetes were enrolled. The control group consisted of 65 STEMI patients without diabetes. All patients received emergency medical services for reperfusion therapy in less than 12 hours after onset of AMI. Blinded to patient clinical characteristics, monocyte subset analysis was performed using flow cytometry immediately after admission. mRNA of Chemokine Decoy Receptor D6 in each subset of monocytes was validated by Q-PCR. Expression of CCL2 in patient plasma was determined with an Elisa kit. Infarct size and left ventricular ejection fraction (LVEF) were measured using 3-dimensional echocardiography 3 days and 6 months after AMI. The incidences of recurrent cardiovascular events and death in each group were measured using the Kaplan-Meier estimator in follow-up during the next 24 months. Cox proportional-hazard models were further used to analyze the relationship of monocyte cell counts and event-free survival after adjusting for confounding factors.The number of circulating intermediate monocytes was significantly correlated with LVEF% and infarct size (r = -0.32; P = 0.008; r = 0.57, P < 0.001) in STEMI patients with diabetes compared with those without diabetes 6 months after AMI. Chemokine Decoy Receptor D6 transcript levels were lower in intermediate monocytes of STEMI patients with diabetes compared to the subsets in STEMI patients without diabetes (P < 0.001). Higher levels of CCL2 (pg/mL) were observed in STEMI patients with diabetes compared to STEMI patients without diabetes (P < 0.001). During a mean follow-up period of 24 ± 1 month, recurrent cardiovascular events or death occurred in 23 patients belonging to the STEMI with diabetes group and 10 belonging to the control group. Univariate Kaplan-Meier analysis revealed that counts of the intermediate monocytes according to median showed statistical significance in STEMI patients with diabetes (P = 0.010). After full adjustment for confounding factors, the cells were found to remain independently related to recurrent cardiovascular events or death in this group (P = 0.004, 95% CI: 1.62-12.49).Intermediate monocytes were associated with LV remodelling in STEMI patients with diabetes. The cells were predictive for recurrent cardiovascular events or death in these patients. A low level of D6 mRNA in the intermediate monocytes of STEMI patients with diabetes and high level of CCL2 in these patients may partially explain the causality.

摘要

本研究旨在评估中间型单核细胞(CD14(++)CD16(+))与糖尿病合并ST段抬高型心肌梗死(STEMI)患者心肌重塑之间的潜在关联。共纳入67例糖尿病合并STEMI患者。对照组由65例非糖尿病STEMI患者组成。所有患者在急性心肌梗死(AMI)发作后12小时内接受了紧急医疗服务以进行再灌注治疗。在患者入院后立即采用流式细胞术进行单核细胞亚群分析,对患者的临床特征进行盲法评估。采用Q-PCR法验证各单核细胞亚群中趋化因子诱饵受体D6的mRNA。用酶联免疫吸附测定(ELISA)试剂盒测定患者血浆中CCL2的表达水平。在AMI后3天和6个月采用三维超声心动图测量梗死面积和左心室射血分数(LVEF)。采用Kaplan-Meier估计量测量每组在接下来24个月随访期间复发性心血管事件和死亡的发生率。进一步采用Cox比例风险模型分析在调整混杂因素后单核细胞计数与无事件生存期之间的关系。与AMI后6个月的非糖尿病STEMI患者相比,糖尿病合并STEMI患者循环中间型单核细胞的数量与LVEF%和梗死面积显著相关(r = -0.32;P = 0.008;r = 0.57,P < 0.001)。与非糖尿病STEMI患者的亚群相比,糖尿病合并STEMI患者中间型单核细胞中趋化因子诱饵受体D6转录水平较低(P < 0.001)。与非糖尿病STEMI患者相比,糖尿病合并STEMI患者的CCL2(pg/mL)水平更高(P < 0.001)。在平均24±1个月的随访期内,糖尿病合并STEMI组的23例患者和对照组的10例患者发生了复发性心血管事件或死亡。单因素Kaplan-Meier分析显示,糖尿病合并STEMI患者中根据中位数计算的中间型单核细胞计数具有统计学意义(P = 0.010)。在对混杂因素进行全面调整后,发现这些细胞与该组复发性心血管事件或死亡仍独立相关(P = 0.004,95%CI:1.62 - 12.49)。中间型单核细胞与糖尿病合并STEMI患者的左心室重塑有关。这些细胞可预测这些患者的复发性心血管事件或死亡。糖尿病合并STEMI患者中间型单核细胞中D6 mRNA水平较低以及这些患者中CCL2水平较高可能部分解释了其中的因果关系。

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