{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T21:21:24Z","timestamp":1785532884099,"version":"3.56.0"},"reference-count":32,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2016,2,23]],"date-time":"2016-02-23T00:00:00Z","timestamp":1456185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31440052"],"award-info":[{"award-number":["31440052"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81400311"],"award-info":[{"award-number":["81400311"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31130030"],"award-info":[{"award-number":["31130030"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Major Basic Research Development Program of China","award":["2012CB517806"],"award-info":[{"award-number":["2012CB517806"]}]},{"name":"Major Basic Research Development Program of China","award":["2013CB933801"],"award-info":[{"award-number":["2013CB933801"]}]},{"name":"Major Basic Research Development Program of China","award":["2011CB503904"],"award-info":[{"award-number":["2011CB503904"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The study was designed to investigate whether endogenous sulfur dioxide (SO2) plays a role in vascular calcification (VC) in rats and its possible mechanisms. In vivo medial vascular calcification was induced in rats by vitamin D3 and nicotine for four weeks. In vitro calcification of cultured A7r5 vascular smooth muscle cells (VSMCs) was induced by calcifying media containing 5 mmol\/L CaCl2. Aortic smooth muscle (SM) \u03b1-actin, runt-related transcription factor 2 (Runx2), transforming growth factor-\u03b2 (TGF-\u03b2) and Smad expression was measured. VC rats showed dispersed calcified nodules among the elastic fibers in calcified aorta with increased aortic calcium content and alkaline phosphatase (ALP) activity. SM \u03b1-actin was markedly decreased, but the osteochondrogenic marker Runx2 concomitantly increased and TGF-\u03b2\/Smad signaling was activated, in association with the downregulated SO2\/aspartate aminotransferase (AAT) pathway. However, SO2 supplementation successfully ameliorated vascular calcification, and increased SM \u03b1-actin expression, but inhibited Runx2 and TGF-\u03b2\/Smad expression. In calcified A7r5 VSMCs, the endogenous SO2\/AAT pathway was significantly downregulated. SO2 treatment reduced the calcium deposits, calcium content, ALP activity and Runx2 expression and downregulated the TGF-\u03b2\/Smad pathway in A7r5 cells but increased SM \u03b1-actin expression. In brief, SO2 significantly ameliorated vascular calcification in association with downregulation of the TGF-\u03b2\/Smad pathway.<\/jats:p>","DOI":"10.3390\/ijms17030266","type":"journal-article","created":{"date-parts":[[2016,2,23]],"date-time":"2016-02-23T10:57:06Z","timestamp":1456225026000},"page":"266","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Endogenous Sulfur Dioxide Inhibits Vascular Calcification in Association with the TGF-\u03b2\/Smad Signaling Pathway"],"prefix":"10.3390","volume":"17","author":[{"given":"Zhenzhen","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Peking University First Hospital, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqian","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University First Hospital, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbao","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University First Hospital, Beijing 100034, China"},{"name":"Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical and Health Sciences, Link\u00f6ping University, Link\u00f6ping 58183, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoshu","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing 100191, China"},{"name":"Department of Physiology and Pathophysiology, Peking University Health Science Centre, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongfen","family":"Qi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfang","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University First Hospital, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1161\/CIRCRESAHA.110.234914","article-title":"Arterial calcification in chronic kidney disease: Key roles for calcium and phosphate","volume":"109","author":"Shanahan","year":"2011","journal-title":"Circ. 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