Identification of serum biomarkers and therapeutic targets for aortic diseases in obesity through multi-omics analysis.

Abstract

Background: Obesity is associated with an increased risk of aortic diseases and operative risks. Currently, there are no effective drugs available to prevent the occurrence and progression of aortic aneurysms or dissections. We investigated potential biomarkers and therapeutic targets using a multi-omics approach.

Methods: Clinical data from 237 patients with aortic disease were analyzed based on body mass index (BMI) to explore the relationship between BMI and clinical outcomes. An obesity mouse model was developed by feeding a high fat diet (HFD), and an aortic disease model was established by administering human angiotensin II (AngII) at a dosage of 1,000 ng/min/kg via osmotic minipumps. Through analysis of murine aortic transcriptomics and serum proteomics, we identified potential biomarkers for aortic disease with obesity. Enzyme-linked immunosorbent assay was used to detect these biomarkers in human serum.

Results: This study analyzed a cohort of 237 patients with aortic disease and 72 patients with valvulopathy. Patients with aortic disease exhibited a significantly higher BMI and a lower mean age compared to those with valvulopathy. Among the aortic disease group, elevated BMI was associated with a younger age, increased systolic and diastolic blood pressure, and a higher percentage of neutrophils. Transcriptomic analysis revealed an enrichment of genes related to complement and coagulation cascades, as well as the prion disease pathway. Proteomic analysis showed an enrichment of proteins associated with African trypanosomiasis and the estrogen signaling pathway. By integrating transcriptomic and proteomic profiles, complement component 5 (C5) and apolipoprotein D (apoD) were identified as potential biomarkers for the adverse effects of obesity.

Conclusions: High BMI is associated with an increased risk of aortic disease, particularly aortic dissection. Serum C5 and apoD have been identified as potential biomarkers for evaluating the risk of aortic disease in obese individuals. Further research is necessary to explore the pathophysiological pathways correlated with these biomarkers and their potential clinical applications.