Metabolic Reprogramming of the Neovascular Niche Promotes Regenerative Angiogenesis in Proliferative Retinopathy
bioRxiv (Cold Spring Harbor Laboratory)(2023)
摘要
Healthy blood vessels supply neurons to preserve metabolic function. In blinding ischemic proliferative retinopathies (PRs), pathological neovascular tufts often emerge in lieu of needed physiological neuroretina revascularization. We show that metabolic shifts in the neurovascular niche define this angiogenic dichotomy between healthy and diseased blood vessel growth. Fatty acid oxidation (FAO) metabolites accumulated in human and murine retinopathy samples. Neovascular tufts with a distinct single-cell transcriptional signature highly expressed FAO enzymes. The deletion of Sirt3, an FAO regulator, shifted the neurovascular niche metabolism from FAO to glycolysis and suppressed tuft formation. This metabolic transition increased Vegf expression in astrocytes and reprogrammed pathological EC to a physiological phenotype, hastening vascular regeneration of the ischemic retina. Our findings identify SIRT3 as a metabolic switch in the neurovascular niche, offering a new therapeutic target for optimizing ischemic tissue revascularization.
### Competing Interest Statement
The authors have declared no competing interest.
更多查看译文
关键词
retinopathy,metabolic
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要