The Role Of Alpha-2-Macroglobulin And Heparin Cofactor Ⅱ In Carotid Atherosclerosis:An ITRAQ-based Quantitative Proteomic Analysis

Objective: Carotid atherosclerosis is a well-known risk factor for cerebrovascular disease, but there is few biomarker in clinic for its evaluation. This study aimed to screen the differentially expressed proteins in the plasmas of patients with carotid atherosclerosis compared with the normal controls, and to explore potential biomarkers and therapy targets.Methods: The 95 participants were divided into three groups(normal controls, low risk group, and high risk group) according to plaque morphology by high resolution ultrasound, and iTRAQ labeling coupled with liquid chromatography-tandem mass spectrometry(LC-MS/MS) was carried out to identify the differentially expressed plasma proteins in the 3 groups. Expressions of selected proteins were validated using ELISA to assess their clinical relevance with high risk carotid plaques. Participants were grouped according to IMT tertiles(<0.8 mm, 0.8-0.9mm, ≥1mm), plaque risk(normal controls, low risk and high risk) and total PS(0, 1, ≥2), then we performed statistical analysis.Results: A total of 28 proteins were identified as differentially expressed in our study. The expression of α2M and HCⅡ were further validated by ELISA, the results were consistent with i TRAQ. With the increasing of α2M concentration, higher incidence of high-risk plaque, carotid intima-media thickening and high total PS were find using ordinal logistic regression model, while HCⅡ had just the opposite correlation with carotid atherosclerosis.Conclusions: Our results indicate that blood α2M may be a risk factor for carotid atherosclerosis, while blood HCⅡ probably act as protective factor.