Sodium thiosulfate acts as a hydrogen sulfide mimetic to prevent intimal hyperplasia via inhibition of tubulin polymerisation
| Autor: | Macabrey, Diane, Longchamp, Alban, MacArthur, Michael R., Lambelet, Martine, Urfer, Severine, Deglise, Sebastien, Allagnat, Florent |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Male
Hyperplasia Proliferation Myocytes Smooth Muscle Animals Cell Proliferation Cystathionine gamma-Lyase/metabolism Humans Hydrogen Sulfide/metabolism Hydrogen Sulfide/pharmacology Hyperplasia/pathology Mice Myocytes Smooth Muscle/metabolism Thiosulfates Tubulin/metabolism Hydrogen sulfide Intimal hyperplasia Smooth muscle cells Sodium thiosulfate Cystathionine gamma-Lyase Tubulin cardiovascular system Hydrogen Sulfide |
| Zdroj: | EBioMedicine, vol. 78, pp. 103954 eBioMedicine, 78 |
| ISSN: | 2352-3964 |
| Popis: | Background Intimal hyperplasia (IH) remains a major limitation in the long-term success of any type of revascularisation. IH is due to vascular smooth muscle cell (VSMC) dedifferentiation, proliferation and migration. The gasotransmitter Hydrogen Sulfide (H2S), mainly produced in blood vessels by the enzyme cystathionine- γ-lyase (CSE), inhibits IH in pre-clinical models. However, there is currently no H2S donor available to treat patients. Here we used sodium thiosulfate (STS), a clinically-approved source of sulfur, to limit IH. Methods Low density lipoprotein receptor deleted (LDLR−/−), WT or Cse-deleted (Cse−/−) male mice randomly treated with 4 g/L STS in the water bottle were submitted to focal carotid artery stenosis to induce IH. Human vein segments were maintained in culture for 7 days to induce IH. Further in vitro studies were conducted in primary human vascular smooth muscle cells (VSMCs). Findings STS inhibited IH in WT mice, as well as in LDLR−/− and Cse−/− mice, and in human vein segments. STS inhibited cell proliferation in the carotid artery wall and in human vein segments. STS increased polysulfides in vivo and protein persulfidation in vitro, which correlated with microtubule depolymerisation, cell cycle arrest and reduced VSMC migration and proliferation. Interpretation STS, a drug used for the treatment of cyanide poisoning and calciphylaxis, protects against IH in a mouse model of arterial restenosis and in human vein segments. STS acts as an H2S donor to limit VSMC migration and proliferation via microtubule depolymerisation. eBioMedicine, 78 ISSN:2352-3964 |
| Databáze: | OpenAIRE |
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