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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.
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.
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）发展的确切机制仍未完全确定。在这项研究中,我们采用了一种利用非靶向蛋白质组学和代谢组学的综合方法来描述HFpEF患者与健康对照组相比的蛋白质组学和代谢组学变化.
方法：数据来自由30名HFpEF参与者和30名健康对照者组成的前瞻性队列，性别和年龄相匹配。血浆样本通过多组学平台进行分析.使用基于数据独立采集的液相色谱-串联质谱（LC-MS/MS）和超高效液相色谱-串联质谱（UHPLC-MS/MS）进行血浆蛋白和代谢物的定量，分别。此外,蛋白质组学和代谢组学结果分别分析，并使用相关性和途径分析进行整合。随后进行了基因本体论（GO）和京都基因和基因组百科全书（KEGG）途径富集研究，以阐明观察到的结果的生物学相关性。
结果：共鉴定出46种显着差异表达的蛋白质（DEP）和102种差异表达的代谢物（DEM）。然后，通过DEP和DEM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着富集，其中DEP和DEM富集。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中不同的炎症和免疫应答途径，突出新颖的治疗途径。
方法：数据来自由30名HFpEF参与者和30名健康对照者组成的前瞻性队列，性别和年龄相匹配。血浆样本通过多组学平台进行分析.使用基于数据独立采集的液相色谱-串联质谱（LC-MS/MS）和超高效液相色谱-串联质谱（UHPLC-MS/MS）进行血浆蛋白和代谢物的定量，分别。此外,蛋白质组学和代谢组学结果分别分析，并使用相关性和途径分析进行整合。随后进行了基因本体论（GO）和京都基因和基因组百科全书（KEGG）途径富集研究，以阐明观察到的结果的生物学相关性。
结果：共鉴定出46种显着差异表达的蛋白质（DEP）和102种差异表达的代谢物（DEM）。然后，通过DEP和DEM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着富集，其中DEP和DEM富集。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中不同的炎症和免疫应答途径，突出新颖的治疗途径。
