Abstract: BACKGROUND: The pathogenesis of coronary heart disease is complex. A single omics approach is limited in elucidating its biological pathways, whereas multi-omics integration helps reveal molecular interaction networks across different levels, addressing the limitations of single-omics methods.
OBJECTIVE: To investigate the pathological mechanisms of coronary heart disease in a mouse model using proteomics and metabolomics.
METHODS: Healthy SPF-grade 8-week-old male C57BL/6 mice were randomly divided into a sham operation group and a model group. The mouse model of coronary heart disease was established by ligation of the left anterior descending coronary artery, while the sham operation group underwent threading without ligation. At 28 days post-surgery, cardiac function was assessed by echocardiography, and myocardial infarct size was evaluated by TTC staining. Ultra-high-performance liquid chromatography-tandem mass spectrometry was employed to screen differentially expressed proteins and metabolites between groups for integrated omics analysis.
RESULTS AND CONCLUSION: (1) Compared with the sham operation group, the model group exhibited significantly decreased cardiac function, with reduced left ventricular ejection fraction and fractional shortening (P < 0.05), and a significantly increased myocardial infarction area (P < 0.01). (2) Proteomics identified 420 differentially expressed proteins, including 282 upregulated (e.g., Serum amyloid A protein, protein kinase D) and 138 downregulated (e.g., Protein YIPF5, E3 ubiquitin-protein ligase). Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that these proteins were mainly involved in ATP-dependent chromatin remodeling and the renin-angiotensin system. (3) Metabolomics identified 155 differential metabolites, with 56 upregulated (e.g., Thromboxane, Tromethamine) and 99 downregulated (e.g., N-Acetyl-D-Tryptophan, D-Xylulose 5-Phosphate). Kyoto Encyclopedia of Genes and Genomes analysis indicate the association between these metabolites and purine metabolism and glycerophospholipid metabolism pathways. (4) Integrated analysis revealed significant correlations between 26 differentially expressed proteins and 16 differential metabolites, involving proteins such as ATP1A3 and Hexokinase, and metabolites such as Cytochalasin B and Gluconasturtiin. To conclude, these findings suggest that the pathogenesis of coronary heart disease may be closely related to disturbances in energy metabolism networks, activation of inflammation-coagulation cascades, and imbalances in ion homeostasis regulation.

Key words: proteomics, metabolomics, coronary heart disease, blood stasis syndrome, biological basis