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心脏手术后血浆血管生成素样蛋白 2 的减少与患者的组织炎症和衰老状态有关。

Reduction of plasma angiopoietin-like 2 after cardiac surgery is related to tissue inflammation and senescence status of patients.

机构信息

Faculty of Medicine, Department of Surgery, Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada.

Montreal Heart Institute Research Center, Université de Montréal, Montreal, Quebec, Canada; Department of Pharmacology, Université de Montréal, Montreal, Quebec, Canada.

出版信息

J Thorac Cardiovasc Surg. 2019 Sep;158(3):792-802.e5. doi: 10.1016/j.jtcvs.2018.12.047. Epub 2019 Jan 8.

Abstract

OBJECTIVES

A strong relationship between high circulating angiopoietin-like 2 (ANGPTL2) levels, a proinflammatory adipokine, and cardiovascular diseases has been reported. Our objective was to determine whether plasma ANGPTL2 and high-sensitivity C-reactive protein (hs-CRP) levels change postoperatively in patients who underwent heart valve surgery and/or coronary artery bypass grafting. We hypothesized that a corrective cardiac surgery would decrease ANGPTL2 levels.

METHODS

In 47 prospectively recruited patients who underwent coronary artery bypass grafting (n = 16), valve replacement (n = 16), or both (n = 15), we measured plasma ANGPTL2 and hs-CRP levels preoperatively, at 24 hours, at 3 to 5 days (hospital discharge), and at 30 to 90 days (follow-up) after surgery. Mediastinal adipose tissue and distal fragments of the left internal mammary artery (IMA) were harvested during surgery and mRNA expression of inflammatory and senescence markers was assessed using real-time quantitative polymerase chain reaction.

RESULTS

ANGPTL2 and hs-CRP levels were elevated 24 hours after surgery and then returned to baseline levels. We noted, however, a dichotomy among patients: compared with baseline, plasma ANGPTL2 levels either significantly decreased (n = 21/47) or increased (n = 26/47) after surgery. In contrast, hs-CRP levels were identical between groups (P = .997). Patients in the increased group were older (P = .002) with a higher systolic blood pressure (P = .038) at baseline. Moreover, changes in ANGPTL2 levels (ΔANGPTL2 = final minus initial levels) positively correlated with mRNA expression of tumor necrosis factor α and interleukin 8 in mediastinal adipose tissue and IMA (P < .05) and with the senescence-associated marker cyclin-dependent kinase inhibitor 1 in IMA (P = .009).

CONCLUSIONS

In younger patients with lower levels of tissue inflammation and arterial senescence load, ANGPTL2, but not hs-CRP levels decreased after cardiac surgery, suggesting that circulating ANGPTL2 reflects tissue inflammation and senescence.

摘要

目的

已有研究报道,高循环血管生成素样 2(ANGPTL2)水平与心血管疾病之间存在密切关系,ANGPTL2 是一种促炎脂肪因子。本研究旨在确定行心脏瓣膜手术和/或冠状动脉旁路移植术的患者术后循环中 ANGPTL2 和高敏 C 反应蛋白(hs-CRP)水平是否发生变化。我们假设纠正性心脏手术会降低 ANGPTL2 水平。

方法

前瞻性招募 47 例拟行冠状动脉旁路移植术(n=16)、瓣膜置换术(n=16)或二者均行(n=15)的患者,于术前、术后 24 小时、35 天(出院时)和 3090 天(随访时)测量血浆 ANGPTL2 和 hs-CRP 水平。手术期间采集纵隔脂肪组织和左内乳动脉(IMA)远端片段,使用实时定量聚合酶链反应评估炎症和衰老标志物的 mRNA 表达。

结果

术后 24 小时 ANGPTL2 和 hs-CRP 水平升高,然后恢复至基线水平。但我们注意到患者存在二分法:与基线相比,术后 ANGPTL2 水平显著降低(n=21/47)或升高(n=26/47)。相比之下,两组间 hs-CRP 水平无差异(P=0.997)。升高组患者年龄较大(P=0.002),基线收缩压较高(P=0.038)。此外,ANGPTL2 水平的变化(ΔANGPTL2=最终水平-初始水平)与纵隔脂肪组织和 IMA 中肿瘤坏死因子-α和白细胞介素 8 的 mRNA 表达呈正相关(P<0.05),与 IMA 中的衰老相关标志物细胞周期蛋白依赖性激酶抑制剂 1 呈正相关(P=0.009)。

结论

在炎症组织和动脉衰老负荷较低的年轻患者中,心脏手术后 ANGPTL2 而非 hs-CRP 水平降低,提示循环 ANGPTL2 反映组织炎症和衰老。

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