Anlar Gulsen Guliz, Pedersen Shona, Al Ashmar Sarah, Krzyslak Hubert, Kamareddine Layla, Zeidan Asad
Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, Qatar.
Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark.
Biomol Biomed. 2025 Apr 26;25(6):1280-1292. doi: 10.17305/bb.2024.10111.
Atherosclerosis, a leading cause of coronary artery disease (CAD), is heavily influenced by hypercholesterolemia (HC). Proteomics research has shown promise in identifying biological markers for CAD diagnosis and prognosis. This cross-sectional study aimed to identify novel biomarkers for detecting HC and CAD. Through the analysis of proteome data from healthy controls (n = 45) and patients diagnosed with HC (n = 51) or CAD (n = 32), distinct protein patterns associated with each condition were identified. Significant alterations in protein levels were identified with a false discovery rate (FDR)-corrected q-value of <0.05. Subsequent receiver operating characteristic (ROC) analysis, with an area under the curve (AUC) greater than 0.75, was conducted. CAD patients exhibited significantly increased levels of the cholesterol-metabolizing protein proprotein convertase subtilisin/kexin type 9 (PCSK9) and varied levels of the angiogenesis-related protein stromal-cell-derived factor-1 (SDF-1) compared to controls. In pairwise comparisons among the study groups, 65 proteins showed significant differential expression. Notably, 14 of these proteins had significant correlations with blood cholesterol levels. Additionally, 22 of the identified proteins were associated with CAD or HC pathways, with nine proteins being common to both conditions (APO E, APO E3, MMP-3, PCSK9, SDF-1, APO B, PAFAH, 60 kDa heat shock protein, and TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 fusion). Nevertheless, this is an exploratory study, and validation studies are needed to confirm these potential protein biomarkers for CAD in the context of HC.
动脉粥样硬化是冠状动脉疾病(CAD)的主要病因,受高胆固醇血症(HC)的影响很大。蛋白质组学研究在识别CAD诊断和预后的生物标志物方面显示出前景。这项横断面研究旨在识别检测HC和CAD的新型生物标志物。通过分析来自健康对照(n = 45)以及被诊断为HC(n = 51)或CAD(n = 32)患者的蛋白质组数据,确定了与每种情况相关的独特蛋白质模式。当错误发现率(FDR)校正后的q值<0.05时,确定蛋白质水平有显著变化。随后进行了曲线下面积(AUC)大于0.75的受试者工作特征(ROC)分析。与对照组相比,CAD患者胆固醇代谢蛋白前蛋白转化酶枯草杆菌蛋白酶/kexin 9型(PCSK9)水平显著升高,血管生成相关蛋白基质细胞衍生因子-1(SDF-1)水平有所不同。在研究组之间的两两比较中,65种蛋白质显示出显著差异表达。值得注意的是,其中有14种蛋白质与血液胆固醇水平有显著相关性。此外,所鉴定的22种蛋白质与CAD或HC途径相关,有9种蛋白质在两种情况下都常见(载脂蛋白E、载脂蛋白E3、基质金属蛋白酶-3、PCSK9、SDF-1、载脂蛋白B、血小板活化因子乙酰水解酶、60 kDa热休克蛋白以及转化生长因子-β激活激酶1和丝裂原活化蛋白激酶激酶激酶7结合蛋白1融合体)。然而,这是一项探索性研究,需要进行验证研究以在HC背景下确认这些潜在的CAD蛋白质生物标志物。