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生物信息学分析钙化斑块中衰老诱导基因

姚海鹏, 钱勇江, 王中群^*

江苏大学附属医院心血管内科，镇江 212000

摘要

血管钙化是引起心血管疾病发生的重要病理生理基础，但其机制尚不十分清楚。近些年研究表明，衰老是血管钙化重要诱因之一，参与血管钙化形成和发展。本文旨在研究血管钙化的细胞亚群微环境特征，识别与钙化斑块密切相关的衰老诱导基因(aging/senescence-induced genes, ASIGs)，探索血管钙化各细胞亚群演化轨迹。基于生物信息学方法对来源于3例接受颈动脉内膜剥脱术患者的颈动脉样本单细胞转录组测序数据集(Gene Expression Omnibus数据库：GSE159677)进行细胞分群及注释，利用ASIGs数据集识别出血管钙化相关衰老基因，通过Monocle 3进行拟时序分析ASIGs在细胞亚群中的拟时间趋势，揭示参与血管钙化细胞的演变轨迹。数据集经质量控制后，所有细胞被划分为8个细胞类型，包括B细胞、T细胞、平滑肌细胞、巨噬细胞、内皮细胞、成纤维细胞、肥大细胞、祖细胞。通过ASIGs数据集，筛选出与血管钙化相关的10个ASIGs，分别编码补体C1qA (complement C1qA, C1QA)、超氧化物歧化酶3 (superoxide dismutase 3, SOD3)、溶菌酶(lysozyme, LYZ)、胰岛素样生长因子结合蛋白7 (insulin-like growth factor binding protein-7, IGFBP7)、补体C1qB (complement C1qB, C1QB)、补体C1qC (complement C1qC, C1QC)、血管性血友病因子(von Willebrand factor, vWF)、小窝蛋白1 (Caveolin 1, CAV1)、丛生蛋白(clusterin, CLU)、αB-晶状体蛋白(αB-crystallin, CRYAB)。拟时序分析发现各细胞类型均参与血管钙化进展，同时这些ASIGs可能在细胞演变过程中起着重要作用。综上，AGIS在血管钙化进展中发挥重要作用，其高表达基因可能为血管钙化的早期诊断与治疗提供思路。

关键词： 衰老; 血管钙化; 生物信息学; 拟时序分析

Bioinformatics analysis identifies aging/senescence-induced genes in calcified plaques

YAO Hai-Peng, QIAN Yong-Jiang, WANG Zhong-Qun^*

Department of Cardiology, the Affiliated Hospital of Jiangsu University, Zhenjiang 212000, China

Abstract

Vascular calcification is an important pathophysiological basis of cardiovascular disease with its underlying mechanism unclear. In recent years, studies have shown that aging is one of the risk factors for vascular calcification. The purpose of this study was to investigate the microenvironmental characteristics of vascular calcification, identify aging/senescence-induced genes (ASIGs) closely related to calcified plaques, and explore the evolution trajectory of vascular calcification cell subsets. Based on the bioinformatics method, the single cell transcriptome sequencing data (Gene Expression Omnibus: GSE159677) of carotid artery samples from 3 patients undergoing carotid endarterectomy were grouped and annotated. Vascular calcification-related aging genes were identified by ASIGs data set. The pseudotime trend of ASIGs in cell subsets was analyzed by Monocle 3, and the evolution of vascular calcification cells was revealed. After quality control, all cells were divided into 8 cell types, including B cells, T cells, smooth muscle cells, macrophages, endothelial cells, fibroblasts, mast cells, and progenitor cells. Ten ASIGs related to vascular calcification were screened from the data set of ASIGs, which include genes encoding complement C1qA (C1QA), superoxide dismutase 3 (SOD3), lysozyme (LYZ), insulin-like growth factor binding protein-7 (IGFBP7), complement C1qB (C1QB), complement C1qC (C1QC), Caveolin 1 (CAV1), von Willebrand factor (vWF), clusterin (CLU), and αB-crystallin (CRYAB). Pseudotime analysis showed that all cell subsets were involved in the progression of vascular calcification, and these ASIGs may play an important role in cell evolution. In summary, AGIS plays an important role in the progression of vascular calcification, and these high expression genes may provide ideas for early diagnosis and treatment of vascular calcification.

Key words: Senescence; vascular calcification; bioinformatics; pseudotime analysis

收稿日期：　　录用日期：

通讯作者：王中群　　E-mail: wangtsmc@126.com; wangzhongqun@ujs.edu.cn

引用本文：

姚海鹏, 钱勇江, 王中群. 生物信息学分析钙化斑块中衰老诱导基因[J]. 生理学报 2022; 74 (6): 939-948.

YAO Hai-Peng, QIAN Yong-Jiang, WANG Zhong-Qun. Bioinformatics analysis identifies aging/senescence-induced genes in calcified plaques. Acta Physiol Sin 2022; 74 (6): 939-948 (in Chinese with English abstract).