婴儿血管瘤（IH）是儿童中最常见的良性肿瘤。普萘洛尔是 IH 的一线治疗药物，但普萘洛尔治疗 IH 的潜在机制尚不完全清楚。进行综合转录和代谢分析，以研究普萘洛尔治疗后血管瘤来源的内皮细胞（HemEC）的代谢变化。然后，通过使用 Seahorse XFp 分析仪、蛋白质印迹、免疫组织化学和线粒体功能测定的独立细胞实验进一步验证了这些发现。通过靶向代谢组学鉴定了 34 种差异表达代谢物，包括糖酵解代谢物葡萄糖 6-磷酸、果糖 6-磷酸和果糖 1,6-二磷酸。 KEGG通路富集分析表明，这些代谢物的紊乱与糖代谢相关通路高度相关，包括磷酸戊糖通路、Warburg效应、糖酵解和柠檬酸循环。转录分析显示，代谢相关途径，包括甘氨酸、丝氨酸和苏氨酸代谢、酪氨酸代谢和谷胱甘肽代谢，高度富集。此外，代谢组学和转录组学数据的整合表明，普萘洛尔治疗后，葡萄糖代谢相关途径，特别是糖酵解发生了改变。细胞实验表明，HemEC 表现出比人脐静脉 EC (HUVEC) 更高水平的糖酵解，并且普萘洛尔抑制 HemEC 中的糖酵解。总之，普萘洛尔通过抑制葡萄糖代谢途径，特别是糖酵解来抑制 HemEC 中的葡萄糖代谢。版权所有 © 2023。由 Elsevier Inc. 出版。

Infantile hemangioma (IH) is the most common benign tumor in children. Propranolol is the first-line treatment for IH, but the underlying mechanism of propranolol treatment in IH is not completely understood. Integrated transcriptional and metabolic analyses were performed to investigate the metabolic changes in hemangioma-derived endothelial cells (HemECs) after propranolol treatment. The findings were then further validated through independent cell experiments using a Seahorse XFp analyzer, Western blotting, immunohistochemistry and mitochondrial functional assays. Thirty-four differentially expressed metabolites, including the glycolysis metabolites glucose 6-phosphate, fructose 6-phosphate and fructose 1,6-bisphosphate, were identified by targeted metabolomics. A KEGG pathway enrichment analysis showed that the disturbances in these metabolites were highly related to glucose metabolism-related pathways, including the pentose phosphate pathway, the Warburg effect, glycolysis and the citric acid cycle. Transcriptional analysis revealed that metabolism-related pathways, including glycine, serine and threonine metabolism, tyrosine metabolism, and glutathione metabolism, were highly enriched. Moreover, integration of the metabolomic and transcriptomic data revealed that glucose metabolism-related pathways, particularly glycolysis, were altered after propranolol treatment. Cell experiments demonstrated that HemECs exhibited higher levels of glycolysis than human umbilical vein ECs (HUVECs) and that propranolol suppressed glycolysis in HemECs. In conclusion, propranolol inhibited glucose metabolism in HemECs by suppressing glucose metabolic pathways, particularly glycolysis.Copyright © 2023. Published by Elsevier Inc.