{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:12:28Z","timestamp":1790475148526,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,4,24]],"date-time":"2019-04-24T00:00:00Z","timestamp":1556064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003825","name":"Magyar Tudom\u00e1nyos Akad\u00e9mia","doi-asserted-by":"publisher","award":["11003"],"award-info":[{"award-number":["11003"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Calcification of heart valves is a frequent pathological finding in chronic kidney disease and in elderly patients. Hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) may exert anti\u2010calcific actions. Here we investigated H<jats:sub>2<\/jats:sub>S as an inhibitor of valvular calcification and to identify its targets in the pathogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Effects of H<jats:sub>2<\/jats:sub>S on osteoblastic transdifferentiation of valvular interstitial cells (VIC) isolated from samples of human aortic valves were studied using immunohistochemistry and western blots. We also assessed H2S on valvular calcification in apolipoprotein E\u2010deficient (ApoE<jats:sup>\u2212\/\u2212<\/jats:sup>) mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>In human VIC, H<jats:sub>2<\/jats:sub>S from donor compounds (NaSH, Na<jats:sub>2<\/jats:sub>S, GYY4137, AP67, and AP72) inhibited mineralization\/osteoblastic transdifferentiation, dose\u2010dependently in response to phosphate. Accumulation of calcium in the extracellular matrix and expression of osteocalcin and alkaline phosphatase was also inhibited. RUNX2 was not translocated to the nucleus and phosphate uptake was decreased. Pyrophosphate generation was increased via up\u2010regulating ENPP2 and ANK1. Lowering endogenous production of H<jats:sub>2<\/jats:sub>S by concomitant silencing of cystathionine \u03b3\u2010lyase (CSE) and cystathionine \u03b2\u2010synthase (CBS) favoured VIC calcification. analysis of human specimens revealed higher Expression of CSE in aorta stenosis valves with calcification (AS) was higher than in valves of aortic insufficiency (AI). In contrast, tissue H<jats:sub>2<\/jats:sub>S generation was lower in AS valves compared to AI valves. Valvular calcification in ApoE<jats:sup>\u2212\/\u2212<\/jats:sup> mice on a high\u2010fat diet was inhibited by H<jats:sub>2<\/jats:sub>S.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>The endogenous CSE\u2010CBS\/H<jats:sub>2<\/jats:sub>S system exerts anti\u2010calcification effects in heart valves providing a novel therapeutic approach to prevent hardening of valves.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed section on Hydrogen Sulfide in Biology &amp; Medicine. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v177.4\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v177.4\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14691","type":"journal-article","created":{"date-parts":[[2019,4,24]],"date-time":"2019-04-24T12:34:51Z","timestamp":1556109291000},"page":"793-809","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Hydrogen sulfide inhibits calcification of heart valves; implications for calcific aortic valve disease"],"prefix":"10.1111","volume":"177","author":[{"given":"Katalin \u00c9va","family":"Sikura","sequence":"first","affiliation":[{"name":"HAS\u2010UD Vascular Biology and Myocardial Pathophysiology Research Group Hungarian Academy of Sciences  Debrecen Hungary"},{"name":"Department of Medicine, Faculty 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