title: Endogenous Sulfur Dioxide Inhibits Vascular Calcification in Association with the TGF-β/Smad Signaling Pathway.
abstract: 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) α-actin, runt-related transcription factor 2 (Runx2), transforming growth factor-β (TGF-β) 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 α-actin was markedly decreased, but the osteochondrogenic marker Runx2 concomitantly increased and TGF-β/Smad signaling was activated, in association with the downregulated SO₂/aspartate aminotransferase (AAT) pathway. However, SO₂ supplementation successfully ameliorated vascular calcification, and increased SM α-actin expression, but inhibited Runx2 and TGF-β/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-β/Smad pathway in A7r5 cells but increased SM α-actin expression. In brief, SO₂ significantly ameliorated vascular calcification in association with downregulation of the TGF-β/Smad pathway.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China. zhenzhenli1886@126.com.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China. yaqianhuang@126.com.
authors.forename: Yaqian
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China. junbaodu1@126.com.|Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing 100191, China. junbaodu1@126.com.
authors.forename: Junbao
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping 58183, Sweden. angie.dongliu@gmail.com.
authors.forename: Angie Dong
authors.initials: AD
authors.lastname: Liu
authors.affiliation: Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing 100191, China. tangchaoshu@263.net.cn.|Department of Physiology and Pathophysiology, Peking University Health Science Centre, Beijing 100191, China. tangchaoshu@263.net.cn.
authors.forename: Chaoshu
authors.initials: C
authors.lastname: Tang
authors.affiliation: Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing 100191, China. yongfenqi@163.com.
authors.forename: Yongfen
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China. jinhongfang51@126.com.
authors.forename: Hongfang
authors.initials: H
authors.lastname: Jin
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002114:Calcinosis / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D013458:Sulfur Dioxide / Q000378:metabolism* / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D000199:Actins; D001219:Aspartate Aminotransferases; D002118:Calcium; D050659:Core Binding Factor Alpha 1 Subunit; D051785:Smad Proteins; D013458:Sulfur Dioxide; D016212:Transforming Growth Factor beta; C493717:Runx2 protein, rat; C498862:Acta2 protein, rat
keywords: smooth muscle cell; sulfur dioxide; transforming growth factor-β; vascular calcification