Untargeted metabolomics-based elucidation of metabolic reprogramming mechanisms and pathways following aortic dissection surgery

基于非靶向代谢组学的主动脉夹层手术后代谢重编程机制和通路阐明

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Abstract

BACKGROUND: Postoperative complications persist in acute DeBakey type I aortic dissection (AD) despite surgical advances, yet the underlying metabolic mechanisms remain unexplored. This knowledge gap critically limits targeted interventions. METHODS: Untargeted metabolomics using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was performed on 90 serum samples, including: preoperative AD patients (n = 30), postoperative samples from the same cohort (AT group, n = 30), and healthy controls (HC, n = 30). Multivariate statistics through orthogonal partial least squares-discriminant analysis (OPLS-DA) identified differential metabolites (variable importance in projection [VIP] > 1, P < 0.05), with Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment revealing regulatory networks. RESULTS: Three interconnected mechanisms were identified: Lipid homeostasis remodeling was characterized by activated linoleic acid metabolism (P = 0.0136), which elevated anti-inflammatory epoxy-eicosatrienoic acids (EETs) and suppressed nuclear factor-kappa B (NF-κB) signaling; Energy reprogramming: Pyruvate/tricarboxylic acid (TCA) cycle intermediates synergized with arginine/nitric oxide (NO) pathway to scavenge reactive oxygen species (ROS). CONCLUSIONS: We propose a multifaceted regulatory network centered on lipid remodeling, energy adaptation, and antioxidant defense, providing a multitarget framework for mitigating postoperative complications in AD.

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