Integrating multi-omics and machine learning strategies to explore the “gene-protein-metabolite” network in ischemic heart failure with Qi deficiency and blood stasis syndrome

作者：Jingjing Wei, Aolong Wang, Peng Yu, Yang Sun, Wenjun Wu, Yilin Zhang, Rui Yu, Bin Li, Mingjun Zhu · 发表于：Chinese Medicine · 年份：2025 · DOI：10.1186/s13020-025-01151-9 · 被引用次数：7 · 研究领域：Biochemical Acid Research Studies、Metabolomics and Mass Spectrometry Studies、Cancer, Hypoxia, and Metabolism

BACKGROUND: Ischemic heart failure (IHF) is a multifaceted syndrome associated with significant mortality and high hospitalization rates globally. According to traditional Chinese medicine (TCM) theory, Qi Deficiency and Blood Stasis (QXXY) Syndrome serves as the pathological basis of IHF. This study aims to investigate the biological basis of QXXY syndrome in IHF patients through an integrated multi-omics approach. METHODS: We enrolled 100 participants, comprising 40 IHF patients with QXXY syndrome (IHF-QXXY), 40 IHF patients without QXXY syndrome, and 20 healthy controls. Utilizing an integrated approach combining RNA sequencing (RNA-seq), data-independent acquisition (DIA) proteomics, and targeted metabolomics, we established a comprehensive "gene-protein-metabolite" network for IHF-QXXY syndrome. Candidate biomarkers were identified through machine learning algorithms and further validated using RT-qPCR and targeted proteomics via intelligent parallel reaction monitoring (iPRM). RESULTS: Patients with IHF-QXXY syndrome present with pronounced disruptions in energy metabolism, chronic inflammation, and coagulation abnormalities. The "gene-protein-metabolite" network of IHF-QXXY syndrome comprises six mRNAs, four proteins, and five metabolites. Key pathways involve the activation of neutrophil extracellular traps formation, platelet activation, the HIF-1 signaling pathway, and glycolysis/gluconeogenesis, alongside the suppression of the citrate cycle and oxidative phosphory...