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The morphology of small pulmonary arteries and collagen metabolism were examined. Cultured pulmonary arterial fibroblasts stimulated by transforming growth factor \u03b21 (\n              <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\n              \u2010\u03b21) were used to explore the mechanism. The results showed that in monocrotaline\u2010treated rats, mean pulmonary artery pressure increased markedly, small pulmonary arterial remodeling developed, and collagen deposition in lung tissue and pulmonary arteries increased significantly in association with elevated\n              <jats:styled-content style=\"fixed-case\">SO<\/jats:styled-content>\n              <jats:sub>2<\/jats:sub>\n              content, aspartate aminotransferase (AAT) activity, and expression of AAT1 compared with control rats. Interestingly,\n              <jats:sc>l<\/jats:sc>\n              \u2010aspartate\u2010\u03b2\u2010hydroxamate, an inhibitor of\n              <jats:styled-content style=\"fixed-case\">SO<\/jats:styled-content>\n              <jats:sub>2<\/jats:sub>\n              generation, further aggravated pulmonary vascular collagen remodeling in monocrotaline\u2010treated rats, and inhibition of\n              <jats:styled-content style=\"fixed-case\">SO<\/jats:styled-content>\n              <jats:sub>2<\/jats:sub>\n              in pulmonary artery smooth muscle cells activated collagen accumulation in pulmonary arterial fibroblasts.\n              <jats:styled-content style=\"fixed-case\">SO<\/jats:styled-content>\n              <jats:sub>2<\/jats:sub>\n              donor, however, alleviated pulmonary vascular collagen remodeling with inhibited collagen synthesis, augmented collagen degradation, and decreased\n              <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\n              \u2010\u03b21 expression of pulmonary arteries. Mechanistically, overexpression of AAT1, a key enzyme of\n              <jats:styled-content style=\"fixed-case\">SO<\/jats:styled-content>\n              <jats:sub>2<\/jats:sub>\n              production, prevented the activation of the\n              <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\n              \u2010\u03b2\/type I\n              <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\n              \u2010\u03b2 receptor\/Smad2\/3 signaling pathway and abnormal collagen synthesis in pulmonary arterial fibroblasts. In contrast, knockdown of AAT1 exacerbated Smad2\/3 phosphorylation and deposition of collagen types I and\n              <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content>\n              in\n              <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\n              \u2010\u03b21\u2013treated pulmonary arterial fibroblasts.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Endogenous\n              <jats:styled-content style=\"fixed-case\">SO<\/jats:styled-content>\n              <jats:sub>2<\/jats:sub>\n              plays a protective role in pulmonary artery collagen accumulation induced by monocrotaline via inhibition of the\n              <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\n              \u2010\u03b2\/type I\n              <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\n              \u2010\u03b2 receptor\/Smad2\/3 pathway.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.116.003910","type":"journal-article","created":{"date-parts":[[2016,10,18]],"date-time":"2016-10-18T20:15:06Z","timestamp":1476821706000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":24,"title":["Sulfur Dioxide Protects Against Collagen Accumulation in Pulmonary Artery in Association With Downregulation of the Transforming Growth Factor \u03b21\/Smad Pathway in Pulmonary Hypertensive Rats"],"prefix":"10.1161","volume":"5","author":[{"given":"Wen","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Peking University First Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Die","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University First Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University First Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Ochs","sequence":"additional","affiliation":[{"name":"Feinberg School of Medicine, Northwestern University, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cellular Biology, University of California, San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selena","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cellular Biology, University of California, San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuxu","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University First Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoshu","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China"},{"name":"Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqian","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University First Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbao","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University First Hospital, Beijing, China"},{"name":"Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfang","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University First Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","first-page":"368","article-title":"Diagnosis and management of pulmonary arterial hypertension: implications for care","volume":"51","author":"Levine DJ","year":"2006","unstructured":"Levine DJ. 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