Li Shen, Gao Yuan, Ma Ke, Li Yanan, Liu Chen, Yan Yingxue, Liu Weishi, Liu Hongbing, Li Zhen, Song Bo, Xu Yuming, Xia Zongping
Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
Department of Clinical Systems Biology Laboratories, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
J Transl Int Med. 2021 Dec 31;9(4):294-306. doi: 10.2478/jtim-2021-0044. eCollection 2021 Dec 1.
The nectin cell adhesion molecule 2 (NECTIN2) protein is a cell adhesion molecule involved in lipid metabolism. We aimed to explore the potential role of NECTIN2 in carotid atherosclerosis (CA).
Patients who underwent carotid endarterectomy (CEA) at the First Affiliated Hospital of Zhengzhou University were enrolled in this study. APOE rats fed western or normal diet were used to model early pathological changes in CA. The relationship between patients' lipid indices and plaque severity was assessed using ordinal regression analysis. Mendelian randomisation (MR) analysis was used to determine the causal links between low-density lipoprotein cholesterol (LDL-C) and atherosclerosis. After matching analysis of the single-cell transcriptome and microarray data of carotid plaques, was identified as a key factor affecting CA. The importance of was further verified by immunofluorescence staining of CEA and APOE rat specimens.
A total of 108 patients were included. The traditional lipid indices did not correlate significantly with the plaque severity ( 0.05). provided a strong causal link between LDL-C level and CA (MR effect size >0). Deep-sequencing data illustrated that expression was cell specific. In early-stage CA, expression was increased in endothelial cells; however, in advanced-stage CA, was overexpressed in macrophages located in fibrous caps. APOE rat carotid artery and human carotid plaques modelled the entire atherosclerotic process, showing an upregulation of expression in CA.
Lipid-related protein NECTIN2 is a potential marker in CA progression and can potentially be a new therapeutic target for clinical prevention.
NECTIN细胞黏附分子2（NECTIN2）蛋白是一种参与脂质代谢的细胞黏附分子。我们旨在探讨NECTIN2在颈动脉粥样硬化（CA）中的潜在作用。
本研究纳入了在郑州大学第一附属医院接受颈动脉内膜切除术（CEA）的患者。使用喂食西式或正常饮食的载脂蛋白E（APOE）大鼠来模拟CA的早期病理变化。采用有序回归分析评估患者脂质指标与斑块严重程度之间的关系。使用孟德尔随机化（MR）分析来确定低密度脂蛋白胆固醇（LDL-C）与动脉粥样硬化之间的因果关系。在对颈动脉斑块的单细胞转录组和微阵列数据进行匹配分析后，确定[具体因素]为影响CA的关键因素。通过对CEA和APOE大鼠标本进行免疫荧光染色进一步验证了[具体因素]的重要性。
共纳入108例患者。传统脂质指标与斑块严重程度无显著相关性（P>0.05）。MR分析显示LDL-C水平与CA之间存在强烈的因果关系（MR效应大小>0）。深度测序数据表明[具体因素]的表达具有细胞特异性。在早期CA中，[具体因素]在内皮细胞中表达增加；然而，在晚期CA中，[具体因素]在位于纤维帽的巨噬细胞中过表达。APOE大鼠颈动脉和人类颈动脉斑块模拟了整个动脉粥样硬化过程，显示CA中[具体因素]表达上调。
脂质相关蛋白NECTIN2是CA进展的潜在标志物，可能成为临床预防的新治疗靶点。
