Wei Fangxiang, Rui Haomiao, Bian Rutao, Liu Shunyu
The Second Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, China.
Henan Province Hospital of TCM (The Second Affiliated Hospital of Henan University of Chinese Medicine), Zhengzhou, China.
Medicine (Baltimore). 2025 Jan 3;104(1):e41115. doi: 10.1097/MD.0000000000041115.
This study aims to explore the causal associations of 91 circulating inflammatory proteins with ischemic cardiomyopathy heart failure (ICM), dilated cardiomyopathy heart failure (DCM), and hypertrophic cardiomyopathy heart failure (HCM) to provide new ideas for the study of relevant heart failure mechanisms, adjunctive diagnosis and differentiation, and the clinical application of relevant drug targets. An analysis of the causal relationship between circulating inflammatory proteins and heart failure was conducted via inverse-variance weighted, weighted median estimator (WME), weighted mode (WM), and Mendelian randomization-Egger regression with Mendelian randomization. A Mendelian randomization analysis of 91 circulating inflammatory proteins revealed that natural killer cell receptor 2B4 levels, CXCL-6, fibroblast growth factor 5 levels, and interleukin-10 levels had positive causal relationships with ICM, whereas CX3CL-1, C-X-C motif chemokine 9 levels, interleukin-10 levels, leukemia inhibitory factor receptor levels, and signaling lymphocytic activation molecule levels had negative causal relationships; C-C motif chemokine 20 levels, C-X-C motif chemokine 5 levels, C-X-C motif chemokine 9 levels, fibroblast growth factor 5 levels, and oncostatin-M levels were positively correlated with DCM, whereas eukaryotic translation initiation factor 4E-binding protein 1 levels and Fms-related tyrosine kinase 3 ligand levels were negatively associated with DCM; and the CD40L receptor, Fms-related tyrosine kinase 3 ligand levels, hepatocyte growth factor levels, and sulfotransferase 1A1 levels were negatively associated with HCM. In this study, 9 of the 91 circulating inflammatory proteins were causally related to the ICM (4 positive, 5 negative), 7 were causally related to the DCM (5 positive, 2 negative), and 4 were causally related to the HCM (all negative). This study provides a theoretical foundation for the study of the relevant mechanisms of heart failure, clinical diagnosis, and treatment, as well as potential drug candidates closely related to heart failure.
本研究旨在探讨91种循环炎症蛋白与缺血性心肌病心力衰竭（ICM）、扩张型心肌病心力衰竭（DCM）和肥厚型心肌病心力衰竭（HCM）之间的因果关联，为相关心力衰竭机制研究、辅助诊断与鉴别以及相关药物靶点的临床应用提供新思路。通过逆方差加权、加权中位数估计器（WME）、加权模式（WM）以及孟德尔随机化-埃格回归与孟德尔随机化对循环炎症蛋白与心力衰竭之间的因果关系进行分析。对91种循环炎症蛋白的孟德尔随机化分析显示，自然杀伤细胞受体2B4水平、CXCL-6、成纤维细胞生长因子5水平和白细胞介素-10水平与ICM呈正因果关系，而CX3CL-1、C-X-C基序趋化因子9水平、白细胞介素-10水平、白血病抑制因子受体水平和信号淋巴细胞激活分子水平呈负因果关系；C-C基序趋化因子20水平、C-X-C基序趋化因子5水平、C-X-C基序趋化因子9水平、成纤维细胞生长因子5水平和制瘤素-M水平与DCM呈正相关，而真核翻译起始因子4E结合蛋白1水平和Fms相关酪氨酸激酶3配体水平与DCM呈负相关；CD40L受体、Fms相关酪氨酸激酶3配体水平、肝细胞生长因子水平和磺基转移酶1A1水平与HCM呈负相关。在本研究中，91种循环炎症蛋白中有9种与ICM存在因果关系（4种正相关，5种负相关），7种与DCM存在因果关系（5种正相关，2种负相关），4种与HCM存在因果关系（均为负相关）。本研究为心力衰竭相关机制研究、临床诊断与治疗以及与心力衰竭密切相关的潜在候选药物提供了理论基础。
