Metabolomic Signatures of Spontaneous Isolated Superior Mesenteric Artery Dissection: Indole Derivatives and Lysophospholipids as Novel Biomarkers

Abstract

Spontaneous isolated superior mesenteric artery dissection (SISMAD) is a rare but increasingly recognized vascular disorder that can lead to intestinal dysfunction with severe complications. Currently, no plasma biomarkers, particularly metabolomics-based markers, have been identified for SISMAD. To identify novel plasma biomarkers and potential therapeutic targets for SISMAD and its associated intestinal dysfunction, we analyzed plasma samples from 30 patients with SISMAD and 30 healthy controls. Blood was collected within 72 h of diagnosis. Ultra-high-performance liquid chromatography coupled with orbitrap mass spectrometry was used to profile metabolites, followed by principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) to analyze the data. A total of 123 and 128 metabolites were significantly changed in the positive and negative ion modes, respectively. Notably, tryptophan-related metabolites, including methyl 2-(1H-indol-3-yl) acetate and indole-3-pyruvic acid (IPA), were significantly reduced in the SISMAD group (p < 0.001), with a strong correlation between the two (Corr. = 0.989, p < 0.001). Pathway analysis revealed that glycerophospholipid metabolism was most enriched, primarily driven by lysophospholipids (LPLs), particularly lysophosphatidylethanolamine (LysoPE), which showed the highest fold change and diagnostic accuracy (area under the curve [AUC] = 0.986). This study identifies significant metabolic alterations in SISMAD, including reductions in indole derivatives (methyl 2-(1H-indol-3-yl) acetate and IPA and several LPLs, such as LysoPE, lysophosphatidylcholine (LysoPC), and lysophosphatidylglycerol (LysoPG). These findings highlight potential diagnostic biomarkers and therapeutic targets for SISMAD and its associated intestinal dysfunction, providing a promising avenue for clinical management and intervention.