Identification of Serum Biomarker in Acute Aortic Dissection by Global and Targeted Metabolomics

Background: Acute aortic dissection (AAD) is the most devastating aortic pathology, and the incidence is increasing worldwide. However, the occurrence and development of AAD are unpredictable. A thorough understanding of the serum metabolic landscape through metabolomic analysis may help identify new biomarkers for AAD and offers new insights into its prevention and evaluation. Methods: Nineteen patients with Stanford type A aortic dissection and 20 healthy individuals were enrolled in this study. We use global and targeted mass spectrometry-based metabolomics to investigate the serum metabolomics profiles, and the data were analyzed by principal component analysis and orthogonal partial least squares discriminant analysis. Results: Initial untargeted metabolomics analysis revealed significant changes of lipids and polar metabolites in patients with AAD. Alterations of the phosphatidylcholine metabolic pathway were further observed by targeted metabolomics. Trimethylamine N-oxide (TMAO) levels were obviously increased in patients with AAD compared with controls (P < 0.005), whereas the levels of carnitine (P < 0.005), choline, and betaine (P < 0.05) were decreased. Furthermore, TMAO levels were associated with disease severity in AAD and correlated positively with C-reactive protein levels (r = 0.537, P = 0.018), IL-6 levels (r = 0.546, P = 0.016), D-dimer levels (r = 0.694, P = 0.001), and maximum aortic diameter on admission (r = 0.748, P = 0.002). Conclusions: Patients with AAD showed a predominant and consistent change of metabolites levels, especially the compounds in the phosphatidylcholine metabolic pathway. TMAO could potentially serve as a biomarker for the auxiliary diagnosis and evaluation of AAD.