山西医科大学学报2025，Vol.56Issue(12)：1328-1342,15.DOI:10.13753/j.issn.1007-6611.2025.12.002
心脏代谢蛋白与颅内动脉瘤的因果关系及免疫的中介作用
Causality of cardiometabolic proteins with intracranial aneurysms and the mediating role of immunity
摘要
Abstract
Objective To investigate the causal relationships between cardiometabolic proteins,immunity,and intracranial aneu-rysm(IA)by Mendelian randomization(MR)analysis,and explore the mediating effect of immunity between cardiometabolic proteins and IA by mediator analysis.Methods Statistical data of 257 cardiometabolic proteins were obtained from the IEU open genome-wide association studies(GWAS)database,731 immune cell phenotypes were retrieved from the GWAS Catalog database,and statistical data for IA were acquired from the FinnGen Database.Firstly,two-sample MR was employed to identify causal relationships between cardiometabolic proteins and IA,and between immune cell phenotypes and IA.After identifying cardiometabolic proteins and immune cell phenotypes causally related to IA,MR was further utilized to analyze the causal relationships between cardiometabolic proteins and immune cell phenotypes.Subsequently,a two-step mediation analysis was employed to establish the mediating effect of immune cell phenotypes in the causal relationship between cardiometabolic proteins and IA.The inverse-variance weighted method was used in each step of the analyses,and multiple MR methods and sensitivity analyses were used to ensure the reliability of the results.Results A total of 11 cardiometabolic proteins and 41 immune cell phenotypes showed causal relationships with IA.Further analyses revealed that 8 cardiometabolic proteins were causally associated with 19 immune cell phenotypes.Mediation analysis indicated that tumor necrosis factor receptor 1 and Versican core proteins reduced IA risk by decreasing both the percentage of CD4+CDdim cells among lymphocytes and the percentage of CD4+CDdim cells among leukocytes.Versican core proteins also reduced IA risk by increasing the expression level of CD25 on activated regulatory T cells(mediating effect=15.21%).Pulmonary surfactant-associated protein D reduced IA risk by increasing the percentage of CD28-CD25++CD8bright cells among T cells(mediating effect=66.17%)and the forward scatter-area on human leukocyte antigen-DR+CD4+cells(mediating effect=8.79%).Nodal modulator 1 reduced IA risk by increasing the percentage of CD28-CD25++CD8bright cells among T cells(mediating effect=30.01%),the percentage of memory B cells among lymphocytes(mediating effect=2.23%),the expression level of CD25 on IgD+CD24+B cells(mediating effect=2.72%),and the expres-sion level of CD19 on IgD+CD3bright B cells(mediating effect=4.26%).Conclusion Immunity partially mediates the causal effects of cardiometabolic proteins on IA.This further strengthens the"heart-brain axis"link and lays the foundation for studies on disease prevention and mechanism of IA.关键词
颅内动脉瘤/心脏代谢蛋白/免疫/孟德尔随机化/因果关系/中介/心-脑轴Key words
intracranial aneurysm/cardiometabolic proteins/immunity/Mendelian randomization/causal relationship/mediation/heart-brain axis分类
医药卫生引用本文复制引用
YANG Yuan,ZHU Jiabao,LI Pu..心脏代谢蛋白与颅内动脉瘤的因果关系及免疫的中介作用[J].山西医科大学学报,2025,56(12):1328-1342,15.基金项目
山西省卫生健康委科研项目(202107) （202107）
