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Updated: Jun 30, 2025
07:36
Angiogenesis in the Ischemic Rat Lung
Published on: February 8, 2013
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Sulfide oxidation promotes hypoxic angiogenesis and neovascularization
Roshan Kumar1, Victor Vitvitsky1, Apichaya Sethaudom1
1Department of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA.
Nature Chemical Biology
|March 21, 2024
Summary
Hypoxia upregulates nitric oxide (NO), increasing hydrogen sulfide (H2S) for blood vessel growth. However, blocking H2S oxidation limits this growth, offering a target for inhibiting tumor angiogenesis.
Area of Science:
- Biochemistry
- Molecular Biology
- Physiology
Background:
- Angiogenesis, or new blood vessel formation, is crucial for tissue homeostasis and is dysregulated in conditions like cancer.
- Gas signaling molecules, including nitric oxide (NO) and hydrogen sulfide (H2S), play complex roles in regulating endothelial cell function.
- The metabolic pathways linking these gas signaling molecules to angiogenesis remain incompletely understood.
Purpose of the Study:
- To investigate the metabolic mechanisms by which gas signaling molecules regulate angiogenesis in endothelial cells.
- To explore the role of the transsulfuration pathway and hydrogen sulfide (H2S) biogenesis in hypoxia-induced angiogenesis.
- To determine the impact of sulfide quinone oxidoreductase (SQOR) deficiency on endothelial cell proliferation and neovascularization.
Main Methods:
- Utilized hypoxic conditions to study endothelial cell responses.
- Investigated the reprogramming of the transsulfuration pathway and H2S production.
- Generated and analyzed whole-body and endothelial-specific Sqor-knockout mouse models (WBCreSqorfl/fl and VE-cadherinCre-ERT2Sqorfl/fl).
- Assessed tumor xenograft growth and muscle angiogenesis after femoral artery ligation.
Main Results:
- Hypoxia upregulates nitric oxide (NO) in endothelial cells, which enhances hydrogen sulfide (H2S) production via the transsulfuration pathway.
- Deficiency in SQOR impairs H2S oxidation, synergizing with hypoxia to limit endothelial proliferation by inducing a reductive shift.
- Sqor-knockout mice (both whole-body and endothelial-specific) exhibited reduced tumor mass, angiogenesis, and muscle neovascularization compared to controls.
Conclusions:
- Data reveal critical molecular links between H2S, oxygen (O2), and NO metabolism in regulating endothelial cell behavior.
- SQOR inhibition represents a metabolic vulnerability that can limit endothelial cell proliferation and neovascularization.
- Targeting SQOR offers a potential therapeutic strategy for inhibiting pathological angiogenesis, such as in tumors.
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