Port Wine Birthmark (PWB) is a congenital
vascular malformation in the skin, occurring in 1-3 per 1,000 live births. We recently generated PWB-derived induced pluripotent stem cells (iPSCs) as clinically relevant disease models. The metabolites associated with the pathological phenotypes of PWB-derived iPSCs are unknown, which we aimed to explore in this study. Metabolites were separated by ultra-performance liquid chromatography and were screened with electrospray ionization mass spectrometry. Orthogonal partial least-squares discriminant analysis, multivariate and univariate analysis were used to identify differential metabolites (DMs). KEGG analysis was used for the enrichment of metabolic pathways. A total of 339 metabolites were identified. There were 22 DMs confirmed with 9 downregulated DMs including
sphingosine and 13 upregulated DMs including
glutathione in PWB iPSCs as compared to controls. Pathway enrichment analysis confirmed the upregulation of
glutathione and downregulation of
sphingolipid metabolism in PWB-derived iPSCs as compared to normal ones. We next examined the expression patterns of the key factors associated with
glutathione metabolism in PWB lesions. We found that
hypoxia-inducible factor 1α (HIF1α),
glutathione S-transferase Pi 1 (GSTP1), γ-glutamyl
transferase 7 (GGT7), and
glutamate cysteine ligase modulatory subunit (GCLM) were upregulated in PWB vasculatures as compared to blood vessels in normal skins. Our data demonstrate that there are perturbations in
sphingolipid and cellular redox homeostasis in the PWB vasculature, which may facilitate cell survival and pathological progression. Our data imply that upregulation of
glutathione may contribute to
laser-resistant phenotypes in the PWB vasculature.