{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T01:41:45Z","timestamp":1790041305320,"version":"4.0.1"},"reference-count":33,"publisher":"American Physiological Society","issue":"2","funder":[{"name":"NIH","award":["HL113303"],"award-info":[{"award-number":["HL113303"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2017,8,1]]},"abstract":"<jats:p> Recent reports have revealed that hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) exerts critical actions to promote cardiovascular homeostasis and health. Thiosulfate is one of the products formed during oxidative H<jats:sub>2<\/jats:sub>S metabolism, and thiosulfate has been used extensively and safely to treat calcific uremic arteriopathy in dialysis patients. Yet despite its significance, fundamental questions regarding how thiosulfate and H<jats:sub>2<\/jats:sub>S interact during redox signaling remain unanswered. In the present study, we examined the effect of exogenous thiosulfate on hypoxia-induced H<jats:sub>2<\/jats:sub>S metabolite bioavailability in human umbilical vein endothelial cells (HUVECs). Under hypoxic conditions, we observed a decrease of GSH and GSSG levels in HUVECs at 0.5 and 4 h as well as decreased free H<jats:sub>2<\/jats:sub>S and acid-labile sulfide and increased bound sulfide at all time points. Treatment with exogenous thiosulfate significantly decreased the ratio of GSH\/GSSG to total sulfide of HUVECs under 0.5 h of hypoxia but significantly increased this ratio in HUVECs under 4 h of hypoxia. These responses reveal that thiosulfate has different effects at low and high doses and under different O<jats:sub>2<\/jats:sub> tensions. In addition, treatment with thiosulfate also diminished VEGF-induced cystathionine-\u03b3-lyase expression and reduced VEGF-induced HUVEC proliferation under both normoxic and hypoxic conditions. These results indicate that thiosulfate can modulate H<jats:sub>2<\/jats:sub>S metabolites and signaling under various culture conditions that impact angiogenic activity. Thus, thiosulfate may serve as a unique sulfide donor to modulate endothelial responses under pathophysiological conditions involving angiogenesis. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY This report provides new evidence that different levels of exogenous thiosulfate dynamically change discrete sulfide biochemical metabolite bioavailability in endothelial cells under normoxia or hypoxia, acting in a slow manner to modulate sulfide metabolites. Moreover, our findings also reveal that thiosulfate surprisingly inhibits VEGF-dependent endothelial cell proliferation associated with a reduction in cystathionine-\u03b3-lyase protein levels. <\/jats:p>","DOI":"10.1152\/ajpheart.00723.2016","type":"journal-article","created":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T20:40:34Z","timestamp":1495831234000},"page":"H256-H264","source":"Crossref","is-referenced-by-count":30,"title":["Role of thiosulfate in hydrogen sulfide-dependent redox signaling in endothelial cells"],"prefix":"10.1152","volume":"313","author":[{"given":"Anna","family":"Leskova","sequence":"first","affiliation":[{"name":"Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibile","family":"Pardue","sequence":"additional","affiliation":[{"name":"Department of Pathology and Translational Pathobiology, Louisiana 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