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.