微血管组织在组织灌注和气体与代谢产物交换中起关键作用。本研究使用人类血管器官样体（BVOs）作为微血管的模型。BVOs完整地再现了人类微血管的关键特征，包括成熟内皮细胞对糖酵解代谢的依赖性，这是通过代谢通量测定和基于质谱的代谢组学技术使用稳定示踪的13C-葡萄糖得出的结论。使用两种化学抑制剂对PFKFB3进行药理学靶向治疗，导致BVOs快速重组，血管退化，周细胞覆盖减少。PFKFB3突变体BVOs也显示类似的结构重塑。BVO分泌物组学分析显示细胞外基质重塑以及CTGF等旁分泌介质的差异表达。重组CTGF的治疗恢复了微血管结构。本研究证明，BVOs在代谢变化的应答中迅速发生结构重组，并鉴定了CTGF作为微血管完整性的关键旁分泌调节因子。© 2023. Springer Nature Limited.

The microvasculature plays a key role in tissue perfusion and exchange of gases and metabolites. In this study we use human blood vessel organoids (BVOs) as a model of the microvasculature. BVOs fully recapitulate key features of the human microvasculature, including the reliance of mature endothelial cells on glycolytic metabolism, as concluded from metabolic flux assays and mass spectrometry-based metabolomics using stable tracing of 13C-glucose. Pharmacological targeting of PFKFB3, an activator of glycolysis, using two chemical inhibitors results in rapid BVO restructuring, vessel regression with reduced pericyte coverage. PFKFB3 mutant BVOs also display similar structural remodelling. Proteomic analysis of the BVO secretome reveal remodelling of the extracellular matrix and differential expression of paracrine mediators such as CTGF. Treatment with recombinant CTGF recovers microvessel structure. In this work we demonstrate that BVOs rapidly undergo restructuring in response to metabolic changes and identify CTGF as a critical paracrine regulator of microvascular integrity.© 2023. Springer Nature Limited.