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冠状动脉旁路手术后与心房颤动相关的术前血浆生物标志物。

Preoperative plasma biomarkers associated with atrial fibrillation after coronary artery bypass surgery.

机构信息

Center for Basic Medical Research and Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.

Center for Basic Medical Research and Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China; Department of Cardiac Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, China; School of Pharmacy, Wannan Medical College, Wuhu, Anhui, China; Department of Surgery, Oregon Health and Science University, Portland, Ore.

出版信息

J Thorac Cardiovasc Surg. 2021 Sep;162(3):851-863.e3. doi: 10.1016/j.jtcvs.2020.01.079. Epub 2020 Feb 19.

Abstract

OBJECTIVES

Postoperative atrial fibrillation (POAF) is a common complication in coronary artery bypass grafting (CABG) procedures. This prospective study aimed to investigate predisposition of proteins and metabolites correlated to POAF after CABG and related cellular pathways.

METHODS

Preoperative plasma samples from patients undergoing CABG procedures were prospectively collected. After CABG, the patients were grouped to POAF or sinus rhythm (N = 170; n = 90 in the discovery set and n = 80 in the validation set). The plasma samples were analyzed using proteomics, metabolomics, and bioinformatics to identify the differential proteins and differential metabolites. The correlation between differential proteins and POAF was also investigated by multivariable regression analysis and receiver operator characteristic analysis.

RESULTS

In the POAF(+) group, 29 differential proteins and 61 differential metabolites were identified compared with the POAF(-) group. The analysis of integrated omics revealed that preoperative alteration of peroxisome proliferators-activated receptor α and glutathione metabolism pathways increased the susceptibility of POAF after CABG. There was a correlation between plasma levels of apolipoprotein-C3, phospholipid transfer protein, glutathione peroxidase 3, cholesteryl ester transfer protein, and POAF.

CONCLUSIONS

The present study for first time at multi-omics levels explored the mechanism of POAF and validated the results in a new cohort of patients, suggesting preexisting differential proteins and differential metabolites in the plasma of patients prone to POAF after CABG. Dysregulation of peroxisome proliferators-activated receptor α and glutathione metabolism pathways related to metabolic remodeling and redox imbalance-associated electrical remodeling may play a key role in the pathogenesis of POAF. Lower plasma phospholipid transfer protein, apolipoprotein-C3, higher cholesteryl ester transfer protein and glutathione peroxidase 3 levels are linked with POAF. These proteins/metabolites may be developed as biomarkers to predict POAF.

摘要

目的

术后心房颤动(POAF)是冠状动脉旁路移植术(CABG)后的常见并发症。本前瞻性研究旨在探讨与 CABG 后 POAF 相关的蛋白质和代谢物的易感性及其相关的细胞途径。

方法

前瞻性收集行 CABG 手术的患者术前血浆样本。CABG 后,将患者分为 POAF 或窦性心律(N=170;发现组 n=90,验证组 n=80)。使用蛋白质组学、代谢组学和生物信息学分析方法分析血浆样本,以鉴定差异蛋白和差异代谢物。还通过多变量回归分析和接收者操作特征分析研究差异蛋白与 POAF 的相关性。

结果

与 POAF(-)组相比,POAF(+)组中鉴定出 29 个差异蛋白和 61 个差异代谢物。综合组学分析表明,过氧化物酶体增殖物激活受体α和谷胱甘肽代谢途径的术前改变增加了 CABG 后 POAF 的易感性。载脂蛋白-C3、磷脂转移蛋白、谷胱甘肽过氧化物酶 3、胆固醇酯转移蛋白和 POAF 的血浆水平之间存在相关性。

结论

本研究首次在多组学水平上探讨了 POAF 的发病机制,并在新的患者队列中验证了结果,提示 CABG 后易发生 POAF 的患者血浆中存在差异蛋白和差异代谢物。与代谢重塑和氧化还原失衡相关的电重塑相关的过氧化物酶体增殖物激活受体α和谷胱甘肽代谢途径的失调可能在 POAF 的发病机制中起关键作用。较低的血浆磷脂转移蛋白、载脂蛋白-C3、较高的胆固醇酯转移蛋白和谷胱甘肽过氧化物酶 3 水平与 POAF 相关。这些蛋白质/代谢物可能被开发为预测 POAF 的生物标志物。

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