FMO2 promotes angiogenesis via regulation of N-acetylornithine

This study identified Flavin Containing Monooxygenase 2 (FMO2) as a pivotal regulator under multiple ischemia circumstances. Targeted EC compensation of FMO2 in genetic ablation model proves its pro-angiogenic function in various ischemic models as well as in developing retina. Metabolomics combining EC single-cell sequencing unveil N-acetylornithine as the top-rank altered metabolite catalyzed by FMO2 which inactivates NOTCH1 expression through the transcriptome regulation of Activating transcription factor 3 (ATF3). Surprisingly, N-acetylornithine delivery displays pro-angiogenic therapeutic effect in the ischemic model. These treating effects from FMO2 and N-acetylornithine can also be recapitulated in human endothelial cells. Our findings provide the pro-angiogenic mechanism underlying FMO2 and its catalyzed metabolite N-acetylornithine, unravel targets for treatment of ischemic diseases. This data shows the methods and materials involved in this research.本研究鉴定出黄素单加氧酶2（Flavin Containing Monooxygenase 2, FMO2）是多种缺血条件下的关键调控因子。在基因敲除模型中对FMO2进行靶向内皮细胞补偿实验，证实了其在多种缺血模型及发育视网膜中具有促血管生成功能。结合内皮细胞单细胞测序的代谢组学分析揭示，N-乙酰鸟氨酸是FMO2催化的排名首位的差异代谢物，其通过调控激活转录因子3（Activating transcription factor 3, ATF3）的转录组，抑制NOTCH1的表达。令人意外的是，递送N-乙酰鸟氨酸在缺血模型中展现出促血管生成的治疗效果。FMO2与N-乙酰鸟氨酸的这些治疗效应，在人内皮细胞中也可得到重现。本研究揭示了FMO2及其催化代谢物N-乙酰鸟氨酸的促血管生成机制，为缺血性疾病的治疗提供了潜在靶点。本数据集涵盖了本研究涉及的实验方法与实验材料。