Abstract
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 (n =160) were compared to normal coronary angiographic subjects (n =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 (n=120, male/femal=61/59) and control (n =120, male/female=60/60). iTRAQ detected 544 proteins with 35 up-regulated and 41 down-regulated (change fold > 1.2 or < 0.83, p < 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 (p < 0.05). There was a positive correlation between these proteins and CAD (p < 0.05) and myocardial infarction history (p < 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.
Highlights
Cardiovascular disease is the leading cause of death all over the world
Changes of plasma proteins have been reported to be correlated with the pathological process of coronary artery disease (CAD) such as inflammation, platelet activation and coagulation [2] and more proteins on CAD have been discovered with proteomic technologies [3, 4]
We have for the first time found in the plasma of coronary artery bypass grafting (CABG) patients that: 1) 35 proteins were up-regulated and 41 were down-regulated; and 2) among the 4 proteins validated in the new group of patients, platelet factor 4 (PF4) and secreted frizzled-related protein 1 (sFRP1) were significantly up-regulated
Summary
Cardiovascular disease is the leading cause of death all over the world. The exact mechanism of CAD remains unclear. Changes of plasma proteins have been reported to be correlated with the pathological process of CAD such as inflammation, platelet activation and coagulation [2] and more proteins on CAD have been discovered with proteomic technologies [3, 4]. Despite of the fact that around 800,000 CAD patients undergo coronary artery bypass grafting (CABG) worldwide annually, the protein profiling of the CABG patients have not been reported. Based on our previous experiences in plasma proteomic studies [6,7,8,9], the present study was designed to identify the protein profiling in triple vessel CAD patients undergoing CABG, in order to detect CAD-related differential proteins in CABG patients by determining the correlations between the specific proteins in the specific disease. The results from the present study may help understanding the pathological processes at the protein level and developing more precise diagnostic and treatment strategy towards “Precision Medicine” in CABG procedures
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