Séance

57 - Séance principale
Oncology and metabolism
3 juin 2021, 17:35 - 19:05, Stream 4: Video Invited, SST, SSCViscérale & ARS

Abstract

3
Video: Sodium thiosulfate, a source of hydrogen sulfide, promotes angiogenesis via inhibition of endothelial cells respiration
D. Macabrey, J. Joniová, A. Longchamp, J.-M. Corpataux, G. Wagnieres, S. Deglise, F. Allagnat, Presenter: F. Allagnat (Lausanne)

Objective
Therapies to accelerate vascular repair are currently lacking. Pre-clinical studies suggest that hydrogen sulfide (H2S), an endogenous gasotransmitter, promotes angiogenesis. Here, we hypothesized that sodium thiosulfate (STS), a clinically relevant H2S donor substance, would stimulate angiogenesis and vascular repair.
Methods
Mouse subjected to hindlimb ischemia were treated systemically with NaHS or STS and leg perfusion was measured by laser Doppler imaging. The pro-angiogenic effect of NaHS or STS was further assessed using a subcutaneous matrigel plug assay and a chick chorioallantoic membrane angiogenesis assay. Migration and proliferation of primary human umbilical endothelial cells (HUVEC) exposed to the same H2S donors were measured using a wound healing assay and BrDU incorporation, respectively. HUVEC respiration and glycolysis were measure in a seahorse apparatus.
Results
STS stimulated arteriogenesis and vascular repair following hindlimb ischemia as evidence by increased laser Doppler imaging and vascular density in the gastrocninemius mucle in wild type C57BL/6J mice. STS also promoted angiogenesis assessed by matrigel plug assay and in the chick chorioallantoic membrane assay. In vitro, both STS and NaHS inhibited mitochondrial respiration and promoted glycolysis in HUVECs, which stimulated cell proliferation and migration and angiogenesis.
Conclusion
STS, a clinically pertinent source of sulfur, promotes angiogenesis and revascularization in a model of hindlimb ischemia. STS probably acts through metabolic reprogramming of endothelial cells toward a more proliferative glycolytic state. These findings may hold broad clinical implications for patients suffering from vascular occlusive diseases.
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