Macabrey Diane, Joniová Jaroslava, Gasser Quentin, Bechelli Clémence, Longchamp Alban, Urfer Severine, Lambelet Martine, Fu Chun-Yu, Schwarz Guenter, Wagnières Georges, Déglise Sébastien, Allagnat Florent
Department of Vascular Surgery, Lausanne University Hospital, Lausanne, Switzerland.
Laboratory for Functional and Metabolic Imaging, LIFMET, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
Front Cardiovasc Med. 2022 Oct 3;9:965965. doi: 10.3389/fcvm.2022.965965. eCollection 2022.
Therapies to accelerate vascular repair are currently lacking. Pre-clinical studies suggest that hydrogen sulfide (HS), an endogenous gasotransmitter, promotes angiogenesis. Here, we hypothesized that sodium thiosulfate (STS), a clinically relevant source of HS, would stimulate angiogenesis and vascular repair. STS stimulated neovascularization in WT and LDLR receptor knockout mice following hindlimb ischemia as evidenced by increased leg perfusion assessed by laser Doppler imaging, and capillary density in the gastrocnemius muscle. STS also promoted VEGF-dependent angiogenesis in matrigel plugs and in the chorioallantoic membrane of chick embryos. , STS and NaHS stimulated human umbilical vein endothelial cell (HUVEC) migration and proliferation. Seahorse experiments further revealed that STS inhibited mitochondrial respiration and promoted glycolysis in HUVEC. The effect of STS on migration and proliferation was glycolysis-dependent. 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.
目前缺乏加速血管修复的疗法。临床前研究表明，内源性气体递质硫化氢（HS）可促进血管生成。在此，我们假设硫代硫酸钠（STS）作为HS的临床相关来源，会刺激血管生成和血管修复。在野生型和低密度脂蛋白受体敲除小鼠后肢缺血后，STS刺激了新血管形成，激光多普勒成像评估的腿部灌注增加以及腓肠肌中的毛细血管密度增加证明了这一点。STS还促进了基质胶栓和鸡胚尿囊绒毛膜中VEGF依赖性血管生成。此外，STS和硫氢化钠刺激了人脐静脉内皮细胞（HUVEC）的迁移和增殖。海马实验进一步表明，STS抑制HUVEC中的线粒体呼吸并促进糖酵解。STS对迁移和增殖的影响依赖于糖酵解。STS可能通过将内皮细胞的代谢重编程为更具增殖性的糖酵解状态来发挥作用。这些发现可能对患有血管闭塞性疾病的患者具有广泛的临床意义。
