Decreased plasma docosahexaenoic acid concentration in chronic obstructive pulmonary disease patients with pulmonary Hypertension: Findings from human lipidomics and transcriptomics analysis

IF 3.2 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta Pub Date : 2024-08-10 DOI:10.1016/j.cca.2024.119899

Lu Wang , Fajiu Li , Shunlian Hu , Yahan Xu , Ziyang Zhu , Wei Qin , Wei Yu , Ying Chen , Tao Wang

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引用次数: 0

Abstract

Oxylipins derived from polyunsaturated fatty acids (PUFAs) are important endogenous signaling molecules, but are little characterized in pulmonary hypertension (PH) due to chronic obstructive pulmonary disease (COPD). In this study, we identified novel plasma oxylipins associated with PH risk in COPD patients. The plasma oxylipin profiles of COPD patients without PH (COPD-noPH) or with PH (COPD-PH) were obtained from discovery and validation cohort, using the process of LC-MS/MS analysis. There was a significant decrease in the plasma levels of both free docosahexaenoic acid (DHA) and DHA-derived oxylipins in the COPD-PH group. The multivariable logistic regression model identified DHA and four DHA-derived oxylipins (13-HDHA, 10-HDHA, 8-HDHA and 16-HDHA) exhibited significant differences between the two groups after adjusting for sex, BMI, FEV1% predicted, and smoking status. The diagnostic value of these metabolites was further evaluated through ROC curve analysis. The transcriptome profiles in peripheral blood mononuclear cells (PBMCs) of COPD-PH patients and COPD-PH patients were detected through high-throughput sequencing. The enrichment analysis revealed that the upregulated differentially expressed genes (DEGs) were highly enriched in the interferon signaling pathway. In addition, DHA supplementation proved that DHA may inhibit the development of pH by reducing the secretion of interferons derived from PBMCs. This conjecture was further confirmed by the higher level of serum interferon-γ and interferon-α2 of COPD-PH patients than that of COPD-noPH patients. The present study highlights that decreased DHA and DHA-derived oxylipins levels are suggestive of a higher risk of pH development in COPD cases.

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患有肺动脉高压的慢性阻塞性肺病患者血浆中二十二碳六烯酸浓度降低：人体脂质组学和转录组学分析结果。

从多不饱和脂肪酸（PUFA）中提取的氧脂素是重要的内源性信号分子，但在慢性阻塞性肺疾病（COPD）引起的肺动脉高压（PH）中却鲜有发现。在这项研究中，我们发现了与 COPD 患者 PH 风险相关的新型血浆氧脂。通过 LC-MS/MS 分析，我们从发现队列和验证队列中获得了无 PH（COPD-noPH）或有 PH（COPD-PH）的 COPD 患者的血浆氧脂谱。在 COPD-PH 组中，血浆中游离的二十二碳六烯酸（DHA）和 DHA 衍生的氧脂素水平均明显下降。多变量逻辑回归模型发现，在调整性别、体重指数、预测 FEV1% 和吸烟状况后，DHA 和四种 DHA 衍生的氧脂素（13-HDHA、10-HDHA、8-HDHA 和 16-HDHA）在两组间存在显著差异。通过 ROC 曲线分析进一步评估了这些代谢物的诊断价值。通过高通量测序检测了 COPD-PH 患者和 COPD-PH 患者外周血单核细胞（PBMC）的转录组图谱。富集分析显示，上调的差异表达基因（DEG）高度富集于干扰素信号通路。此外，补充 DHA 还证明，DHA 可通过减少 PBMCs 干扰素的分泌来抑制 pH 的发展。COPD-PH 患者血清中干扰素-γ 和干扰素-α2 的水平高于 COPD-noPH 患者，进一步证实了这一猜想。本研究强调，DHA 和 DHA 衍生的氧脂素水平降低表明 COPD 患者出现 pH 的风险较高。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinica Chimica Acta 医学-医学实验技术

CiteScore

10.10

自引率

2.00%

发文量

1268

审稿时长

23 days

期刊介绍： The Official Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Clinica Chimica Acta is a high-quality journal which publishes original Research Communications in the field of clinical chemistry and laboratory medicine, defined as the diagnostic application of chemistry, biochemistry, immunochemistry, biochemical aspects of hematology, toxicology, and molecular biology to the study of human disease in body fluids and cells. The objective of the journal is to publish novel information leading to a better understanding of biological mechanisms of human diseases, their prevention, diagnosis, and patient management. Reports of an applied clinical character are also welcome. Papers concerned with normal metabolic processes or with constituents of normal cells or body fluids, such as reports of experimental or clinical studies in animals, are only considered when they are clearly and directly relevant to human disease. Evaluation of commercial products have a low priority for publication, unless they are novel or represent a technological breakthrough. Studies dealing with effects of drugs and natural products and studies dealing with the redox status in various diseases are not within the journal''s scope. Development and evaluation of novel analytical methodologies where applicable to diagnostic clinical chemistry and laboratory medicine, including point-of-care testing, and topics on laboratory management and informatics will also be considered. Studies focused on emerging diagnostic technologies and (big) data analysis procedures including digitalization, mobile Health, and artificial Intelligence applied to Laboratory Medicine are also of interest.