European journal of medical research · 2025
Untargeted metabolomics-based elucidation of metabolic reprogramming mechanisms and pathways following aortic dissection surgery.
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He Jun, Xiao Yuji, Ma Wanru, Feng Yaoguang, Ding Chengming, Zhang Haonan, Yang Heng, Lei Zhengwen
Аннотация
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.
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.