Sulfide oxidation promotes hypoxic angiogenesis and neovascularization.

ABSTRACT: Angiogenic programming in the vascular endothelium is a tightly regulated process for maintaining tissue homeostasis and is activated in tissue injury and the tumor microenvironment. The metabolic basis of how gas signaling molecules regulate angiogenesis is elusive. Here, we report that hypoxic upregulation of ·NO in endothelial cells reprograms the transsulfuration pathway to increase biogenesis of hydrogen sulfide (H₂S), a proangiogenic metabolite. However, decreased H₂S oxidation due to sulfide quinone oxidoreductase (SQOR) deficiency synergizes with hypoxia, inducing a reductive shift and limiting endothelial proliferation that is attenuated by dissipation of the mitochondrial NADH pool. Tumor xenografts in whole-body (WB^CreSqor^fl/fl) and en

SUBMITTER: Kumar R 

PROVIDER: S-EPMC11584973 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature