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剖析免疫细胞、血浆代谢物与冠状动脉粥样硬化之间的因果关系：一项孟德尔随机化研究

Dissecting Causal Relationship Among Immune Cells, Plasma Metabolites and Coronary Atherosclerosis: A Mendelian Randomization Study.

作者信息

Cao Qi, Liu Jiajing, Sun Jingyu, Qian Shuangshuang, Song Junhuai, Zheng Haoyang, Wen Jinkun, Zheng Bin

机构信息

Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, 050017, People's Republic of China.

出版信息

Immunotargets Ther. 2025 Mar 6;14:175-188. doi: 10.2147/ITT.S508042. eCollection 2025.

DOI:10.2147/ITT.S508042
PMID:40066076
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11892494/
Abstract

BACKGROUND

Circulating immune cells and metabolites are linked to coronary atherosclerosis, but the specific causal relationships and the role of metabolites as mediators remain unclear.

METHODS

Summary statistics from GWAS datasets on immune cells (n=3,757), circulating metabolites (n=8,299), and coronary atherosclerosis (cases n=51,589; controls n=343,079) were analyzed using bidirectional Mendelian randomization. Two-step and multivariate Mendelian randomization were employed to identify mediating metabolites, with inverse variance weighting (IVW) as the primary method.

RESULTS

We identified nine immune cell phenotypes, including specific T-cell and monocyte populations, with significant causal links to coronary atherosclerosis. Additionally, 41 plasma metabolites across four metabolic pathways were identified, including 3-hydroxy-2-ethylpropionate and trans-2-hexenoylglycine. Mediation analysis revealed that 3-hydroxy-2-ethylpropionate mediated the effect of IgD+ CD24+ B-cells on coronary atherosclerosis (mediating effect: 0.961; 95% CI: 0.955-0.967), while trans-2-hexenoylglycine regulated IgD+ CD24+ B-cells, showing a mediation ratio of 16.7% (mediating effect: 0.983; 95% CI: 0.981-0.986).

CONCLUSION

Key immune cell phenotypes and plasma metabolites were linked to coronary atherosclerosis. The roles of 3-hydroxy-2-ethylpropionate and trans-2-hexenoylglycine in regulating B-cell function suggest potential therapeutic targets for prevention and treatment.

摘要

背景

循环免疫细胞和代谢产物与冠状动脉粥样硬化有关，但具体的因果关系以及代谢产物作为介质的作用仍不清楚。

方法

使用双向孟德尔随机化分析了关于免疫细胞（n = 3757）、循环代谢产物（n = 8299）和冠状动脉粥样硬化（病例n = 51589；对照n = 343079）的全基因组关联研究（GWAS）数据集的汇总统计数据。采用两步法和多变量孟德尔随机化来识别介导代谢产物，以逆方差加权（IVW）作为主要方法。

结果

我们确定了九种免疫细胞表型，包括特定的T细胞和单核细胞群体，它们与冠状动脉粥样硬化存在显著的因果关系。此外，还确定了四种代谢途径中的41种血浆代谢产物，包括3-羟基-2-乙基丙酸酯和反式-2-己烯酰甘氨酸。中介分析表明，3-羟基-2-乙基丙酸酯介导了IgD + CD24 + B细胞对冠状动脉粥样硬化的影响（中介效应：0.961；95%置信区间：0.955 - 0.967），而反式-2-己烯酰甘氨酸调节IgD + CD24 + B细胞，中介比例为16.7%（中介效应：0.983；95%置信区间：0.981 - 0.986）。

结论

关键免疫细胞表型和血浆代谢产物与冠状动脉粥样硬化有关。3-羟基-2-乙基丙酸酯和反式-2-己烯酰甘氨酸在调节B细胞功能中的作用提示了预防和治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a64/11892494/b728ae8cda4e/ITT-14-175-g0007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a64/11892494/91e1905e1e14/ITT-14-175-g0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a64/11892494/b728ae8cda4e/ITT-14-175-g0007.jpg

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