Sulfide oxidation promotes hypoxic angiogenesis and neovascularization
dc.contributor.author | Kumar, Roshan | |
dc.coverage.spatial | University of Michigan Cancer Center | |
dc.date.accessioned | 2024-07-16T13:07:47Z | |
dc.date.available | 2024-07-16T13:07:47Z | |
dc.date.issued | 2023-12-07 | |
dc.identifier.uri | https://www.ncbi.nlm.nih.gov/pubmed/38509349 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/194104 | en |
dc.description.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 (WBCreSqorfl/fl) and endothelial-specific (VE-cadherinCre-ERT2Sqorfl/fl) Sqor-knockout mice exhibit lower mass and angiogenesis than control mice. WBCreSqorfl/fl mice also exhibit decreased muscle angiogenesis following femoral artery ligation compared to control mice. Collectively, our data reveal the molecular intersections between H2S, O2 and ·NO metabolism and identify SQOR inhibition as a metabolic vulnerability for endothelial cell proliferation and neovascularization. (Figure presented.) | |
dc.description.sponsorship | University of Michigan | |
dc.language | eng | |
dc.subject | 3101 Biochemistry and Cell Biology | |
dc.subject | 31 Biological Sciences | |
dc.subject | Regenerative Medicine | |
dc.subject | Cardiovascular | |
dc.subject | Cardiovascular | |
dc.title | Sulfide oxidation promotes hypoxic angiogenesis and neovascularization | |
dc.type | Presentation | |
dc.identifier.pmid | 38509349 | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/194104/2/Nature Chmical Biology.pdf | |
dc.identifier.doi | 10.1038/s41589-024-01583-8 | |
dc.identifier.doi | https://dx.doi.org/10.7302/23548 | |
dc.date.updated | 2024-07-16T13:07:44Z | |
dc.identifier.orcid | 0000-0002-5372-8682 | |
dc.identifier.name-orcid | Kumar, Roshan; 0000-0002-5372-8682 | |
dc.working.doi | 10.7302/23548 | en |
dc.owningcollname | Biological Chemistry, Department of |
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