循环细胞因子在心力衰竭中的作用:一项双向、双样本孟德尔随机研究。

IF 2.8 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Frontiers in Cardiovascular Medicine Pub Date : 2024-10-22 eCollection Date: 2024-01-01 DOI:10.3389/fcvm.2024.1332015
Haoran Zheng, Xinxin Mao, Zhenyue Fu, Chunmei Chen, Jiayu Lv, Yajiao Wang, Yuxin Wang, Huaqin Wu, Yvmeng Li, Yong Tan, Xiya Gao, Lu Zhao, Xia Xu, Bingxuan Zhang, Qingqiao Song
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引用次数: 0

摘要

背景:细胞因子通过调节炎症反应、促进血管收缩和促进内皮损伤,在心力衰竭(HF)的进展过程中发挥着关键作用。然而,现在很难在观察性研究中区分心力衰竭与细胞因子之间的因果关系。对细胞因子进行孟德尔随机化(MR)分析或许能提高我们对高血压潜在生物学过程的理解:本研究旨在通过 MR 分析探讨 41 种细胞因子与高血脂在遗传水平上的相关性。我们选择了2018年心衰分子流行病学治疗目标(HERMES)的高频数据集和芬兰人细胞因子水平荟萃分析的细胞因子数据集。使用反方差加权(IVW)、加权中位数和MR- egger进行了双样本、双向MR分析,并对结果进行了异质性和多向性检验,随后进行了敏感性分析:结果发现:循环中巨噬细胞炎症原蛋白-1β(MIP-1β)(P = 0.0389)、干扰素γ诱导蛋白10(IP-10)(P = 0.0029)和正常T细胞表达和分泌的激活调节蛋白(RANTES)(P = 0.0120)表达水平高的遗传预测与心房颤动风险升高有关。HF与循环中白细胞介素-2受体α亚基(IL-2ra)(P = 0.0296)、β-神经生长因子(β-NGF)(P = 0.0446)、白细胞介素-17(IL-17)(P = 0.0360)、碱性成纤维细胞生长因子(FGF-basic)(P = 0.0220)、血小板衍生生长因子 BB(PDGF-BB)(P = 0.0466)和干扰素-γ(IFN-γ)(P = 0.0222);Eotaxin 水平降低(P = 0.0133)。除了 FGF-basic 和 IL-17 存在轻微的异质性外,其他细胞因子的异质性和多义性均可接受:这些发现为细胞因子与高房颤动之间的遗传预测关系提供了令人信服的证据,强调了靶向调节细胞因子在延缓高房颤动进展方面的巨大潜力。本研究在基因水平上得出了进一步的结论,为未来的大规模临床试验提供了依据。
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The role of circulating cytokines in heart failure: a bidirectional, two-sample Mendelian randomization study.

Background: Cytokines play a pivotal role in the progression of heart failure (HF) by modulating inflammatory responses, promoting vasoconstriction, and facilitating endothelial injury. However, it is now difficult to distinguish the causal relationship between HF and cytokines in observational studies. Mendelian randomization (MR) analyses of cytokines probably could enhance our comprehension to the underlying biological processes of HF.

Methods: This study was to explore the correlation between 41 cytokines with HF at the genetic level by MR analysis. We selected a HF dataset from the Heart Failure Molecular Epidemiology for Therapeutic Targets (HERMES) 2018 and a cytokine dataset from a meta-analysis of cytokine levels in Finns. Two-sample, bidirectional MR analyses were performed using Inverse Variance Weighted (IVW), Weighted Median and MR- egger, and the results were tested for heterogeneity and pleiotropy, followed by sensitivity analysis.

Results: Genetic prediction of high levels of circulating Macrophage inflammatory pro-tein-1β(MIP-1β) (P = 0.0389), Interferon gamma induced protein 10(IP-10) (P = 0.0029), and Regu-lated on activation, normal T cell expressed and secreted(RANTES) (P = 0.0120) expression was associated with an elevated risk of HF. HF was associated with the increased levels of circulating Interleukin-2 receptor, alpha subunit(IL-2ra) (P = 0.0296), Beta nerve growth fac-tor(β-NGF) (P = 0.0446), Interleukin-17(IL-17) (P = 0.0360), Basic fibroblast growth factor(FGF-basic) (P = 0.0220), Platelet derived growth factor BB(PDGF-BB) (P = 0.0466), and Interferon-gamma(IFN-γ) (P = 0.0222); and with decreased levels of Eotaxin (P = 0.0133). The heterogeneity and pleiotropy of the cytokines were acceptable, except for minor heterogeneity of FGF-basic and IL-17.

Conclusion: These findings provide compelling evidence for a genetically predictive relationship between cytokines and HF, emphasizing a great potential of targeted modulation of cytokines in slowing the progression of HF. This study draws further conclusions at the genetic level, providing a basis for future large-scale clinical trials.

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来源期刊
Frontiers in Cardiovascular Medicine
Frontiers in Cardiovascular Medicine Medicine-Cardiology and Cardiovascular Medicine
CiteScore
3.80
自引率
11.10%
发文量
3529
审稿时长
14 weeks
期刊介绍: Frontiers? Which frontiers? Where exactly are the frontiers of cardiovascular medicine? And who should be defining these frontiers? At Frontiers in Cardiovascular Medicine we believe it is worth being curious to foresee and explore beyond the current frontiers. In other words, we would like, through the articles published by our community journal Frontiers in Cardiovascular Medicine, to anticipate the future of cardiovascular medicine, and thus better prevent cardiovascular disorders and improve therapeutic options and outcomes of our patients.
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