Department of Laboratory Medicine, Institute of Biomedicine (J.S., U.R.), Sahlgrenska Academy, University of Gothenburg, Sweden.
Region Västra Götaland, Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden (J.S., U.R., L.M.H.).
Arterioscler Thromb Vasc Biol. 2021 Mar;41(3):1218-1228. doi: 10.1161/ATVBAHA.120.314720. Epub 2021 Jan 21.
COMP (cartilage oligomeric matrix protein) is abundantly expressed in the cardiovascular system, cartilage, and atherosclerotic plaques. We investigated if the total COMP (COMPtotal) and COMP neoepitope (COMPneo) with other cardiovascular markers and clinical parameters could identify symptomatic carotid stenosis. Approach and Results: Blood samples were collected from patients with symptomatic carotid stenosis (stenosis, n=50), patients with stroke without carotid stenosis but small plaques (plaque, n=50), and control subjects (n=50). COMPtotal and COMPneo were measured using an ELISA. Ninety-two cardiovascular disease markers were measured by the Olink CVD kit. The presence of native COMP and COMPneo was determined by immunohistochemistry. The concentration of COMPneo was higher and COMPtotal was lower in the stenosis group. When the concentration was compared between the stenosis and control groups, IL-1ra (interleukin-1 receptor antagonist protein), IL6 (interleukin-6), REN (Renin), MMP1 (matrix metalloproteinase-1), TRAIL-R2 (tumor necrosis factor-related apoptosis-inducing ligand receptor 2), ITGB1BP2 (integrin beta 1 binding protein 2), and COMPneo were predictive of stenosis. Conversely, KLK6 (kallikrein-6), COMPtotal, NEMO (nuclear factor-kappa-B essential modulator), SRC (Proto-oncogene tyrosine-protein kinase Src), SIRT2 (SIR2-like protein), CD40 (cluster of differentiation 40), TF (tissue factor), MP (myoglobin), and RAGE (receptor for advanced glycation end-products) were predictive of the control group. Model reproducibility was good with the receiver operating characteristic plot area under the curve being 0.86. When comparing the plaque group and stenosis group, COMPneo, GAL (galanin), and PTX3 (pentraxin-related protein PTX3) were predictive of stenosis. Model reproducibility was excellent (receiver operating characteristic plot area under the curve 0.92). COMPneo was detected in smooth muscle-, endothelial-, and foam-cells in carotid stenosis.
Degradation of COMP may be associated with atherosclerosis progression and generation of a specific COMP fragment-COMPneo. This may represent a novel biomarker that together with COMPtotal and other risk-markers could be used to identify symptomatic carotid stenosis. Graphic Abstract: A graphic abstract is available for this article.
软骨寡聚基质蛋白（COMP）在心血管系统、软骨和动脉粥样硬化斑块中大量表达。我们研究了总 COMP（COMPtotal）和 COMP 新表位（COMPneo）与其他心血管标志物和临床参数相结合是否可以识别有症状的颈动脉狭窄。
采集了 50 例有症状颈动脉狭窄（狭窄组）、50 例无颈动脉狭窄但有小斑块的卒中患者（斑块组）和 50 例对照者的血液样本。使用 ELISA 法检测 COMPtotal 和 COMPneo。通过 Olink CVD 试剂盒测定 92 种心血管疾病标志物。通过免疫组织化学法检测天然 COMP 和 COMPneo 的存在。狭窄组中 COMPneo 浓度较高，COMPtotal 浓度较低。当将浓度与狭窄组和对照组进行比较时，白细胞介素 1 受体拮抗剂蛋白（IL-1ra）、白细胞介素 6（IL6）、肾素（REN）、基质金属蛋白酶 1（MMP1）、肿瘤坏死因子相关凋亡诱导配体受体 2（TRAIL-R2）、整合素 β 1 结合蛋白 2（ITGB1BP2）和 COMPneo 具有预测狭窄的作用。相反，激肽释放酶 6（KLK6）、COMPtotal、核因子-κB 必需调节剂（NEMO）、原癌基因酪氨酸蛋白激酶Src（SRC）、SIR2 样蛋白（SIRT2）、CD40（分化簇 40）、组织因子（TF）、肌红蛋白（MP）和晚期糖基化终产物受体（RAGE）具有预测对照组的作用。ROC 曲线下面积表明模型的可重复性较好，为 0.86。当比较斑块组和狭窄组时，COMPneo、甘丙肽（GAL）和 pentraxin 相关蛋白 PTX3（PTX3）具有预测狭窄的作用。模型的可重复性极好（ROC 曲线下面积为 0.92）。在颈动脉狭窄中检测到 COMPneo 存在于平滑肌细胞、内皮细胞和泡沫细胞中。
COMP 的降解可能与动脉粥样硬化的进展和特定 COMP 片段-COMPneo 的产生有关。这可能代表一种新的生物标志物，与 COMPtotal 和其他风险标志物一起可用于识别有症状的颈动脉狭窄。
