# Exploring molecular characteristics and interactions of blood stasis syndrome in ischemic heart failure by integrated multi-omics

## TL;DR

This study uses multi-omics to uncover molecular features and pathways linked to blood stasis syndrome in ischemic heart failure, identifying potential diagnostic and therapeutic targets.

## Contribution

The study introduces an integrated multi-omics approach to reveal core molecular networks and pathways specific to blood stasis syndrome in ischemic heart failure.

## Key findings

- Key pathways include complement and coagulation cascade and B-cell receptor signaling.
- F2, F8, F9, and FN1 are identified as potential diagnostic and therapeutic targets for blood stasis syndrome.
- Metabolic pathways like glycine, arginine, and tryptophan metabolism are involved in blood stasis syndrome.

## Abstract

Ischemic heart failure (IHF) is one of the leading causes of death worldwide. In traditional Chinese medicine, blood stasis syndrome (BSS) is regarded as a core pathological feature of IHF. This study aims to clarify the main biological characteristics and underlying mechanisms of BSS in IHF.

Using an integrated multi-omics strategy combining transcriptomics, proteomics, and targeted metabolomics, we systematically analyzed the molecular characteristics of BSS in patients with IHF from multiple perspectives. By integrating multi-omics data and correlating them with clinical parameters, we identified a core molecular network associated with BSS. Key targets within this network were further validated using iPRM and RT-qPCR. ROC curve analysis and responses to pharmacological intervention were employed to confirm the diagnostic and therapeutic potential of these core molecular targets.

A total of 435 differentially expressed genes, 176 differentially abundant proteins, and 40 differentially altered metabolites related to IHF with BSS were identified. Multi-omics analysis highlighted the involvement of the complement and coagulation cascade and B cell receptor signaling pathway. Moreover, targeted metabolomics suggested that metabolic pathways associated with BSS involve glycine, arginine, tryptophan metabolism, and fatty acid biosynthesis. Integrated multi-omics correlation analysis identified CD79A, CD79B, CD19, CD22, CR2, F2, F8, F9, C3, FN1, 5-hydroxyindolacetic acid, and 4-acetamidobutanoate as core molecular features, with significant correlations observed between these molecules and clinical indicators. iPRM and RT-qPCR validation confirmed that the expression trends of these core molecules are consistent with the sequencing results. Furthermore, cross-validation with Yiqi Huoxue formula intervention identified F2, F8, F9, and FN1 as four diagnostic and therapeutic targets for BSS.

This multi-omics analysis reveals that immune dysregulation, inflammation, and impaired coagulation function are central to BSS in IHF. Key pathways involved include the complement and coagulation cascade as well as B-cell receptor signaling, with F2, F8, F9, and FN1 identified as potential diagnostic and therapeutic targets. These findings provide new molecular insights into BSS in IHF.

Diagram outlining a study on heart failure involving participant enrollment, clinical data collection, and multi-omics analysis. Includes patient groups, diagnostic tests, and analytical methods such as transcriptomics, proteomics, and metabolomics. Venn diagrams, pathway charts, and correlation analyses illustrate findings. Validation methods and interventions are also shown.