Guo Zhi-Peng, Hou Hai-Tao, Jing Rui, Song Zhen-Guo, Liu Xiao-Cheng, He Guo-Wei
Center for Basic Medical Research, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Shi, China.
Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Shi, China.
Oncotarget. 2017 Mar 18;8(36):60528-60538. doi: 10.18632/oncotarget.16366. eCollection 2017 Sep 1.
This study was designed to identify the protein profiling in patients with triple vessel coronary artery disease (CAD) undergoing CABG, in order to detect CAD-related differential proteins in these patients. CABG patients with triple vessel disease with/without left main stenosis ( =160) were compared to normal coronary angiographic subjects ( =160). Plasma samples of 20 males and 20 females in each group were analyzed with iTRAQ technique. ELISA test was used to test the chosen proteins from iTRAQ results in plasma samples from a new cohort of the CABG group (=120, male/femal=61/59) and control ( =120, male/female=60/60). iTRAQ detected 544 proteins with 35 up-regulated and 41 down-regulated (change fold > 1.2 or < 0.83, < 0.05). Three proteins including platelet factor 4 (PF4), coagulation factor XIII B chain (F13B), and secreted frizzled-related protein 1 (sFRP1) were selected for validation by using ELISA that demonstrated significant up-regulation of PF4 and sFRP1 ( < 0.05). There was a positive correlation between these proteins and CAD ( < 0.05) and myocardial infarction history ( < 0.05). Thus, we for the first time have found 76 proteins differentially expressed in plasma of CABG patients. The thrombotic disease/inflammation progress-related protein PF4 and sFRP1, a member of the Wnt/fz signal-transduction pathway and related to myocardial repair, are significantly up-regulated in triple-vessel disease with/without left main stenosis. PF4 may be developed as a biomarker for the diagnosis of the severity of CAD requiring CABG procedure.
本研究旨在确定接受冠状动脉旁路移植术(CABG)的三支血管冠状动脉疾病(CAD)患者的蛋白质谱,以便检测这些患者中与CAD相关的差异蛋白。将伴有/不伴有左主干狭窄的三支血管疾病的CABG患者(n = 160)与冠状动脉造影正常的受试者(n = 160)进行比较。每组中20名男性和20名女性的血浆样本采用iTRAQ技术进行分析。酶联免疫吸附测定(ELISA)试验用于检测来自CABG组新队列(n = 120,男/女= 61/59)和对照组(n = 120,男/女= 60/60)血浆样本中iTRAQ结果所选择的蛋白质。iTRAQ检测到544种蛋白质,其中35种上调,41种下调(变化倍数> 1.2或< 0.83,P < 0.05)。选择包括血小板因子4(PF4)、凝血因子XIII B链(F13B)和分泌型卷曲相关蛋白1(sFRP1)在内的三种蛋白质通过ELISA进行验证,结果显示PF4和sFRP1显著上调(P < 0.05)。这些蛋白质与CAD(P < 0.05)和心肌梗死病史(P < 0.05)之间存在正相关。因此,我们首次发现76种在CABG患者血浆中差异表达的蛋白质。血栓性疾病/炎症进展相关蛋白PF4以及Wnt/fz信号转导通路成员且与心肌修复相关的sFRP1在伴有/不伴有左主干狭窄的三支血管疾病中显著上调。PF4可能被开发成为一种用于诊断需要进行CABG手术的CAD严重程度的生物标志物。