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整合蛋白质组学和代谢组学分析揭示 HFpEF 中炎症和免疫反应的新见解。

Integrated proteomic and metabolomic profiling reveals novel insights on the inflammation and immune response in HFpEF.

机构信息

Department of Heart Failure, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, Xinjiang, China.

出版信息

BMC Genomics. 2024 Jul 8;25(1):676. doi: 10.1186/s12864-024-10575-w.

DOI:10.1186/s12864-024-10575-w
PMID:38977985
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11229282/
Abstract

BACKGROUND

The precise mechanisms leading to the development of heart failure with preserved ejection fraction (HFpEF) remain incompletely defined. In this study, an integrative approach utilizing untargeted proteomics and metabolomics was employed to delineate the altered proteomic and metabolomic profiles in patients with HFpEF compared to healthy controls.

MATERIALS AND METHODS

Data were collected from a prospective cohort consisting of 30 HFpEF participants and 30 healthy controls, matched by gender and age. plasma samples were analyzed by multi-omics platforms. The quantification of plasma proteins and metabolites was performed using data-independent acquisition-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) and ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), respectively. Additionally, Proteomic and metabolomic results were analyzed separately and integrated using correlation and pathway analysis. This was followed by the execution of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment studies to elucidate the biological relevance of the observed results.

RESULTS

A total of 46 significantly differentially expressed proteins (DEPs) and 102 differentially expressed metabolites (DEMs) were identified. Then, GO and KEGG pathway enrichment analyses were performed by DEPs and DEMs. Integrated analysis of proteomics and metabolomics has revealed Tuberculosis and African trypanosomiasis pathways that are significantly enriched and the DEPs and DEMs enriched within them, are associated with inflammation and immune response.

CONCLUSIONS

Integrated proteomic and metabolomic analyses revealed distinct inflammatory and immune response pathways in HFpEF, highlighting novel therapeutic avenues.

摘要

背景

导致射血分数保留的心力衰竭(HFpEF)发展的确切机制仍不完全明确。在这项研究中,采用了一种整合的方法,利用非靶向蛋白质组学和代谢组学来描绘 HFpEF 患者与健康对照组相比,蛋白质组学和代谢组学图谱的改变。

材料和方法

数据来自一个前瞻性队列,包括 30 名 HFpEF 参与者和 30 名健康对照者,按性别和年龄匹配。通过多组学平台分析血浆样本。使用基于数据非依赖性采集的液相色谱-串联质谱(LC-MS/MS)和超高效液相色谱-串联质谱(UHPLC-MS/MS)分别对血浆蛋白和代谢物进行定量。此外,分别对蛋白质组学和代谢组学结果进行分析,并通过相关性和途径分析进行整合。然后,进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)途径富集研究,以阐明观察结果的生物学相关性。

结果

共鉴定出 46 个差异表达蛋白(DEPs)和 102 个差异表达代谢物(DEMs)。然后,通过 DEPs 和 DEMs 进行 GO 和 KEGG 途径富集分析。蛋白质组学和代谢组学的综合分析揭示了结核病和非洲锥虫病途径显著富集,其中富集的 DEPs 和 DEMs 与炎症和免疫反应有关。

结论

整合的蛋白质组学和代谢组学分析揭示了 HFpEF 中独特的炎症和免疫反应途径,突出了新的治疗途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6272/11229282/22ef908f8910/12864_2024_10575_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6272/11229282/ca8735bbe24e/12864_2024_10575_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6272/11229282/fff4fa2d6798/12864_2024_10575_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6272/11229282/22ef908f8910/12864_2024_10575_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6272/11229282/ca8735bbe24e/12864_2024_10575_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6272/11229282/fff4fa2d6798/12864_2024_10575_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6272/11229282/22ef908f8910/12864_2024_10575_Fig3_HTML.jpg

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