Comprehensive Metabolic Profiling of Inflammation Indicated Key Roles of Glycerophospholipid and Arginine Metabolism in Coronary Artery Disease.
Comprehensive Metabolic Profiling of Inflammation Indicated Key Roles of Glycerophospholipid and Arginine Metabolism in Coronary Artery Disease.
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炎症的综合代谢分析表明甘油磷脂和精氨酸代谢在冠状动脉疾病中的关键作用
DOI：
10.3389/fimmu.2022.829425
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发表时间：
2022
影响因子：
7.3
通讯作者：
Zhong S
中科院分区：
文献类型：
--
作者：
Zhu Q;Wu Y;Mai J;Guo G;Meng J;Fang X;Chen X;Liu C;Zhong S
全身性免疫炎症是冠状动脉疾病（CAD）进展的关键介质，涉及各种代谢和脂质变化。在这项研究中，炎症指数和代谢之间的关系与CAD患者进行了调查，以提供深入了解炎症相关的代谢紊乱。对1，234名CAD患者进行了广泛针对性的血浆代谢组学和脂质组学分析。实验室循环炎症标志物主要用于定义全身免疫和低度炎症状态。采用多元校正线性回归分析860种代谢物与7种炎症标志物之间的相关性。应用最小绝对收缩和选择运算符（LASSO）基于逻辑的分类器和多变量逻辑回归来识别炎症状态的生物标志物并开发用于区分晚期炎症状态的模型。多种代谢物和脂质种类与七种炎症标志物线性相关[错误发现率（FDR）<0.05]。LASSO和多变量校正logistic回归分析发现45种代谢物与全身免疫炎症指数、46种代谢物与嗜中性粒细胞-淋巴细胞比率状态、32种代谢物与低度炎症评分、26种代谢物与高敏C反应蛋白状态显著相关（P < 0.05）。甘油磷脂代谢以及精氨酸和脯氨酸代谢被确定为全身免疫和低度炎症状态的关键改变的代谢途径。仅基于代谢物组合的预测模型显示了区分代表炎症状态的四个参数的可行性（曲线下面积：0.81至0.88），并使用验证队列成功验证。炎症相关代谢产物β-假尿苷与颈动脉和冠状动脉硬化指标相关（P < 0.05）。这项研究提供了进一步的信息之间的关系，血浆代谢产物谱和炎症状态所代表的各种炎症标志物在CAD。这些代谢标志物为CAD进展期间的病理变化提供了潜在的见解，并可能有助于开发治疗靶点。
Systemic immune inflammation is a key mediator in the progression of coronary artery disease (CAD), concerning various metabolic and lipid changes. In this study, the relationship between the inflammatory index and metabolic profile in patients with CAD was investigated to provide deep insights into metabolic disturbances related to inflammation. Widely targeted plasma metabolomic and lipidomic profiling was performed in 1,234 patients with CAD. Laboratory circulating inflammatory markers were mainly used to define general systemic immune and low-grade inflammatory states. Multivariable-adjusted linear regression was adopted to assess the associations between 860 metabolites and 7 inflammatory markers. Least absolute shrinkage and selection operator (LASSO) logistic-based classifiers and multivariable logistic regression were applied to identify biomarkers of inflammatory states and develop models for discriminating an advanced inflammatory state. Multiple metabolites and lipid species were linearly associated with the seven inflammatory markers [false discovery rate (FDR) <0.05]. LASSO and multivariable-adjusted logistic regression analysis identified significant associations between 45 metabolites and systemic immune-inflammation index, 46 metabolites and neutrophil–lymphocyte ratio states, 32 metabolites and low-grade inflammation score, and 26 metabolites and high-sensitivity C-reactive protein states (P < 0.05). Glycerophospholipid metabolism and arginine and proline metabolism were determined as key altered metabolic pathways for systemic immune and low-grade inflammatory states. Predictive models based solely on metabolite combinations showed feasibility (area under the curve: 0.81 to 0.88) for discriminating the four parameters that represent inflammatory states and were successfully validated using a validation cohort. The inflammation-associated metabolite, namely, β-pseudouridine, was related to carotid and coronary arteriosclerosis indicators (P < 0.05). This study provides further information on the relationship between plasma metabolite profiles and inflammatory states represented by various inflammatory markers in CAD. These metabolic markers provide potential insights into pathological changes during CAD progression and may aid in the development of therapeutic targets.
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DOI：
10.1161/01.atv.0000184758.07257.88
发表时间：
2005-11-01
影响因子：
8.7
作者：
Choi, JH;Nam, KH;Oh, GT
通讯作者：
Oh, GT
影响因子：
5.4
作者：
Doroszko, Adrian;Andrzejak, Ryszard;Szuba, Andrzej
通讯作者：
Szuba, Andrzej
影响因子：
3.7
作者：
Carneiro AB;Iaciura BM;Nohara LL;Lopes CD;Veas EM;Mariano VS;Bozza PT;Lopes UG;Atella GC;Almeida IC;Silva-Neto MA
通讯作者：
Silva-Neto MA
影响因子：
6.5
作者：
Glaros, Elias N.;Kim, Woojin S.;Garner, Brett
通讯作者：
Garner, Brett
影响因子：
4.6
作者：
Hasegawa, S.;Ichiyama, T.;Furukawa, S.
通讯作者：
Furukawa, S.