单细胞核转录组测序揭示阿司匹林抑制川崎病小鼠模型心脏组织的血管新生  

Single-cell nuclear transcriptome sequencing reveals aspirin inhibits angiogenesis in Kawasaki disease mouse model

作　　者：王晶晶 俞海国[2] 樊志丹[2] WANG Jing-jing;YU Hai-guo;FAN Zhi-dan(Department of Cardiovascular Medicine,Henan Provincial Chest Hospital&Chest Hospital Affiliated to Zhengzhou University,Zhengzhou 450003,China;Department of Rheumatology and Immunology,Children′s Hospital of Nanjing Medical University,Nanjing 210008,China)

机构地区：[1]河南省胸科医院心血管内科,郑州大学附属胸科医院,河南郑州450003 [2]南京医科大学附属儿童医院,风湿免疫科,江苏南京210008

出　　处：《药学学报》2024年第10期2809-2819,共11页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(82271838)。

摘　　要：川崎病(Kawasaki disease,KD)是一种主要发生在儿童的急性全身性血管炎疾病。如果在疾病发作早期未给予及时的治疗,可能会导致冠状动脉扩张或形成动脉瘤,严重者可引起心肌梗死。川崎病的发病机制与免疫细胞浸润冠状动脉壁有关。巨噬细胞在川崎病发展中扮演关键角色,参与炎症反应和血管新生。血管内皮生长因子(vascular endothelial growth factor,VEGF)在川崎病患者血清和冠状动脉中表达上调,促进炎症和血管生成,增加动脉瘤的风险。阿司匹林(aspirin,ASA)是川崎病常规治疗方法之一,其主要作用是通过减少炎性介质和抑制血小板聚集来发挥抗炎和抗血栓作用。研究中实验动物的动物福利和动物实验过程均遵循南京医科大学附属儿童医院医学伦理委员会的伦理指南。单细胞核转录组测序技术(single-nucleus RNA sequencing,snRNA-seq)可以深入到川崎病细胞和分子层面的图景探索,本文通过snRNA-seq分析得到,阿司匹林可通过下调心脏血管内皮细胞VEGF水平并抑制巨噬细胞向内皮传导血管新生信号,来改善血管内皮功能失调、阻止血管新生,进而防止动脉狭窄或动脉瘤形成。Kawasaki disease(KD)is an acute systemic vasculitis that primarily affects children.If left untreated in the early stages of the disease,it can lead to coronary artery aneurysms or the formation of arterial fistulae,and in severe cases,myocardial infarction.The pathogenesis of KD is related to the infiltration of immune cells into the walls of the coronary arteries.Macrophages play a crucial role in the development of KD by participating in inflammatory responses and neovascularization.Vascular endothelial growth factor(VEGF)is upregulated in the serum and coronary arteries of patients with KD,promoting inflammation and neovascularization,thereby increasing the risk of aneurysms.Aspirin is one of the standard treatment methods for KD.It exerts antiinflammatory and anti-thrombotic effects by inhibiting platelet aggregation and reducing inflammatory mediators,thus controlling the acute symptoms of the disease.Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Children′s Hospital of Nanjing Medical University.Single-cell nuclear transcriptome sequencing(snRNA-seq)can provide profound insights into the cellular and molecular landscape of KD.Through snRNA-seq analysis,it was found that aspirin may improve endothelial dysfunction by downregulating VEGF levels in coronary endothelial cells and inhibiting macrophage-mediated proangiogenic signals to endothelial cells,thereby preventing arterial stenosis or aneurysm formation.

关 键 词：川崎病 冠状动脉 血管新生 血管内皮生长因子 巨噬细胞 

分 类 号：R966[医药卫生—药理学]