Metabolic reprogramming in aortic diseases: insights from metabolomics and therapeutic opportunities

Aortic diseases (aortic aneurysm, aortic dissection, atherosclerosis) represent a substantial clinical and economic burden due to the lack of effective early diagnostic tools and mechanism-based therapies. Metabolomics, the systematic study of low-molecular-weight metabolites, has emerged as a powerful approach for elucidating pathogenesis, screening candidate biomarkers, and discovering novel drug targets. Rather than merely cataloging metabolic perturbations, this review highlights how metabolic reprogramming, particularly involving amino acid pathways, mitochondrial dysfunction, and gut microbiota-derived metabolites, actively drives aortic pathology. While specific metabolites (e.g., succinate and trimethylamine N-oxide) show promises as prognostic biomarkers, their greatest value lies in revealing actionable therapeutic nodes. Although challenges remain regarding metabolite identification, biological heterogeneity, and clinical translation, continued technological advances and integrative multi-omics approaches offer clear pathways to overcome these barriers. Ultimately, we posit that prioritizing these convergent metabolic axes, especially the gut-vascular interface, could unlock next-generation precision therapies that transcend the limitations of conventional hemodynamic management.