Integrated analysis of metabolomic and transcriptomic profiles elucidates the core role of glycerophospholipid metabolism in hypertension related to metabolic syndrome

Background

Metabolic syndrome (MetS) represents a comprehensive framework that encompasses conditions such as diabetes, hypertension (HBP), obesity, and dyslipidemia. MetS without hypertension significantly contributes to the development of refractory hypertension. However, the underlying molecular regulatory mechanisms of hypertension associated with MetS remain incompletely elucidated. The objective of this study was to identify differences in plasma metabolome and leukocyte transcriptome profiles between patients with MetS comorbid HBP compared to those with MetS with hypertension and HBP alone.

Methods

In this study, whole blood samples were collected from 104 participants, including patients with HBP, MetS without hypertension (MS), and MetS with hypertension (MS-HBP). Ultra-high-performance liquid chromatography was employed to perform metabolomic analysis of plasma samples. Comparative analysis was conducted to identify distinct metabolites among the three groups, while MetaboAnalyst 5.0 was utilized for enrichment and pathway analysis. Clinical correlation analysis and receiver operating characteristic analyses were applied to select biomarker metabolites for MS-HBP. Transcriptomic profiling of white blood cells was performed to identify dysregulated genes and KEGG/GO pathways. Integrative analysis of metabolomics and transcriptomics was used to construct molecular interaction networks. Finally, blood pressure was monitored every 2 weeks during the treatment period for experimental validation.

Results

The metabolomic results indicated that lipid metabolic pathways, particularly glycerophospholipid metabolic pathways, played a crucial role in MS-HBP. The area under the curve of tryptophan-isoleucine for diagnosis in the MS-HBP group was 0.82. Tryptophyl-isoleucine demonstrated a negative correlation with both HbA1c and diastolic blood pressure. Transcriptomic analysis revealed the involvement of MS-HBP in numerous immune and inflammatory pathways. Furthermore, the integrated analysis of metabolomic and transcriptomic data emphasized the importance of glycerophospholipid metabolism in MS-HBP. PPC exhibited a comparable effect on lowering blood pressure in SHR rats.

Conclusion

The findings of this study demonstrated that glycerophospholipid metabolism plays a pivotal role in the pathophysiological processes of MS-HBP, providing novel insights into early clinical diagnosis and the optimization of therapeutic strategies.