{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:54:30Z","timestamp":1793318070729,"version":"4.5.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,8,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Heterozygous mutation in BMP (bone morphogenetic protein) receptor 2 is rare, but BMP cascade suppression is common in congenital heart disease\u2013associated pulmonary arterial hypertension (CHD\u2010PAH); however, the underling mechanism of BMP cascade suppression independent of BMP receptor 2 mutation is unknown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">Pulmonary hypertensive status observed in CHD\u2010PAH was surgically reproduced in rats. Gremlin\u20101 expression was increased, but BMP cascade was suppressed, in lungs from CHD\u2010PAH patients and shunted rats, whereas shunt correction retarded these trends in rats. Immunostaining demonstrated increased gremlin\u20101 was mainly in the endothelium and media of remodeled pulmonary arteries. However, mechanical stretch time\u2010 and amplitude\u2010dependently stimulated gremlin\u20101 secretion and suppressed BMP cascade in distal pulmonary arterial smooth muscle cells from healthy rats. Under static condition, gremlin\u20101 significantly promoted the proliferation and inhibited the apoptosis of distal pulmonary arterial smooth muscle cells from healthy rats via BMP cascade. Furthermore, plasma gremlin\u20101 closely correlated with hemodynamic parameters in CHD\u2010PAH patients and shunted rats.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Serving as an endogenous antagonist of BMP cascade, the increase of gremlin\u20101 in CHD\u2010PAH may present a reasonable mechanism explanation for BMP cascade suppression independent of BMP receptor 2 mutation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.120.016586","type":"journal-article","created":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T09:12:25Z","timestamp":1596186745000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Vital Roles of Gremlin\u20101 in Pulmonary Arterial Hypertension Induced by Systemic\u2010to\u2010Pulmonary Shunts"],"prefix":"10.1161","volume":"9","author":[{"given":"Liukun","family":"Meng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease Fuwai Hospital National Center for Cardiovascular Disease Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Teng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease Fuwai Hospital National Center for Cardiovascular Disease Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease Fuwai Hospital National Center for Cardiovascular Disease Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Organ Transplantation and Thoracic Surgery The First Affiliated Hospital of Guangzhou Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Center Beijing Anzhen HospitalCapital Medical UniversityBeijing Institute of Heart, Lung and Blood Vascular Diseases Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Yuan","sequence":"additional","affiliation":[{"name":"Medical Research Center Beijing Chao\u2010Yang HospitalCapital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Meng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease Fuwai Hospital National Center for Cardiovascular Disease Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjie","family":"Chi","sequence":"additional","affiliation":[{"name":"Heart Center and Beijing Key Laboratory of Hypertension Research Beijing Chao\u2010Yang HospitalCapital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology Jiangxi Provincial People's Hospital Affiliated to Nanchang University Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7518-1681","authenticated-orcid":false,"given":"Xiaoyan","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical Research Center Beijing Chao\u2010Yang HospitalCapital Medical University Beijing China"},{"name":"Heart Center and Beijing Key Laboratory of Hypertension Research Beijing Chao\u2010Yang HospitalCapital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.10.029"},{"key":"e_1_3_1_3_2","first-page":"295","article-title":"Smooth muscle cell hypertrophy, proliferation, migration and apoptosis in pulmonary hypertension","volume":"1","author":"Taisic T","year":"2011","unstructured":"Taisic T, Morrell NW. 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