Dalian Medical University, Dalian 116024, China; Dalian Municipal Central Hospital Affiliated of Dalian Medical University, Dalian 116033, China.
Dalian Municipal Central Hospital Affiliated of Dalian Medical University, Dalian 116033, China.
Clin Neurol Neurosurg. 2022 Jan;212:107067. doi: 10.1016/j.clineuro.2021.107067. Epub 2021 Nov 25.
Current researches on human carotid atherosclerosis (AS) plaques are focused on vulnerable plaques, and various methods have been clinically used to detect vulnerable plaques to prevent adverse events. GRP78 and CHOP, as markers in the endoplasmic reticulum stress (ERS), have a certain relationship with the stability of plaque tissue.
In this study, 150 plaque specimens were obtained from carotid endarterectomy (CEA). According to pathology, they were divided into two groups: stable plaque and vulnerable plaque. Immunohistochemistry was used to semi-quantitate and localize the target molecule. Western blot and RT-qPCR were used to detect the expression of GRP78 and CHOP in the samples. The receiver operating characteristic curve (ROC curve) judges the significance of the target molecule as a biomarker for the diagnosis of vulnerable plaques.
The results of immunohistochemistry showed that the target molecules of GRP78 and CHOP were mainly expressed in inflammatory cells and vascular endothelial cells; Western blot and RT-qPCR techniques were used to detect the expression of GRP78 and CHOP in different pathlogical types of plaques, which respectively indicated that there were differential expressions. The expression in vulnerable plaques was significantly higher than that in stable plaques (P < 0.05). analysis with ROC, the areas under curves (AUC) of the GRP78 and CHOP data were calculated as 0.792 and 0.850, respectively and the combination showed the largest AUC of 0.870.
In endoplasmic reticulum stress, GRP78 and CHOP are significantly higher expressions in vulnerable plaques than stable's, which indicated that GRP78 and CHOP played a certain role in the occurrence and development of human carotid atherosclerosis and vulnerable plaques; GRP78 and CHOP are promising molecular biomarkers for identifying the endoplasmic reticulum stress situation, atherosclerosis and plaque stability. They also could provide a potential drug targets for the prevention and treatment of atherosclerosis.
目前对人类颈动脉粥样硬化(AS)斑块的研究集中在易损斑块上,临床上已经采用了各种方法来检测易损斑块,以预防不良事件。GRP78 和 CHOP 作为内质网应激(ERS)标志物,与斑块组织稳定性有一定关系。
本研究从颈动脉内膜切除术(CEA)中获得了 150 个斑块标本。根据病理学将其分为两组:稳定斑块和易损斑块。采用免疫组织化学方法对半定量和定位靶分子。采用 Western blot 和 RT-qPCR 检测样本中 GRP78 和 CHOP 的表达。受试者工作特征曲线(ROC 曲线)判断靶分子作为易损斑块诊断标志物的意义。
免疫组织化学结果显示,GRP78 和 CHOP 的靶分子主要在炎症细胞和血管内皮细胞中表达;Western blot 和 RT-qPCR 技术检测不同病理类型斑块中 GRP78 和 CHOP 的表达,分别表明存在差异表达。易损斑块中的表达明显高于稳定斑块(P<0.05)。ROC 分析显示,GRP78 和 CHOP 数据的曲线下面积(AUC)分别计算为 0.792 和 0.850,组合显示最大 AUC 为 0.870。
在内质网应激中,GRP78 和 CHOP 在易损斑块中的表达明显高于稳定斑块,表明 GRP78 和 CHOP 在人类颈动脉粥样硬化和易损斑块的发生发展中起一定作用;GRP78 和 CHOP 是识别内质网应激情况、动脉粥样硬化和斑块稳定性的有前途的分子标志物。它们也可能为动脉粥样硬化的预防和治疗提供潜在的药物靶点。