{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T03:03:55Z","timestamp":1784603035890,"version":"3.55.0"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,8,21]]},"abstract":"\n Background<\/jats:title>\n \n Activin receptor\u2010like kinase 4 (\n ALK<\/jats:styled-content>\n 4) is highly expressed in mammal heart. Atrial fibrillation (\n AF<\/jats:styled-content>\n ) is closely related to ventricular pressure overload. Because pressure overload increases atrial pressure and leads to atrial remodeling, it would be informative to know whether\n ALK<\/jats:styled-content>\n 4 exerts potential effects on atrial remodeling and\n AF<\/jats:styled-content>\n vulnerability in a pressure\u2010overload model.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Wild\u2010type littermates and\n ALK<\/jats:styled-content>\n 4\n +\/\u2212<\/jats:sup>\n mice were subjected to abdominal aortic constriction or a sham operation. After 4 or 8\u00a0weeks, echocardiographic and hemodynamic measurements were performed, and inducibility of\n AF<\/jats:styled-content>\n was tested. The hearts were divided into atria and ventricles and then were fixed in formalin for staining, or they were weighted and snap\u2010frozen for quantitative real\u2010time polymerase chain reaction and Western blot analysis. Compared with wild\u2010type littermates,\n ALK<\/jats:styled-content>\n 4\n +\/\u2212<\/jats:sup>\n mice demonstrated a similar extent of atrial hypertrophy but significantly suppressed atrial fibrosis at 8\u00a0weeks post\u2013abdominal aortic constriction.\n ALK<\/jats:styled-content>\n 4 haplodeficiency partially blocked abdominal aortic constriction\u2013induced upregulation of monocyte chemotactic protein 1 and interleukin\u20106, and the increased chemotaxin of macrophages.\n ALK<\/jats:styled-content>\n 4 haplodeficiency also blunted a reduction of connexin 40 and redistribution of connexin 43 from the intercalated disk to the lateral membranes, thereby improving localized conduction abnormalities. Meanwhile,\n ALK<\/jats:styled-content>\n 4 haplodeficiency inhibited abdominal aortic constriction\u2013induced decreased\n \n I\n N<\/jats:sub>\n <\/jats:styled-content>\n a<\/jats:sub>\n ,\n \n I\n C<\/jats:sub>\n <\/jats:styled-content>\n a\u2010L<\/jats:sub>\n and\n \n I\n K<\/jats:sub>\n <\/jats:styled-content>\n 1<\/jats:sub>\n densities as well as the accompanying action potential duration shortening. Mechanistically,\n ALK<\/jats:styled-content>\n 4 haploinsufficiency resulted in the suppression of Smad2\/3 activity in this model.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Our results demonstrate that\n ALK<\/jats:styled-content>\n 4 haplodeficiency ameliorates atrial remodeling and vulnerability to\n AF<\/jats:styled-content>\n in a pressure\u2010overload model through inactivation of the Smad2\/3 pathway, suggesting that\n ALK<\/jats:styled-content>\n 4 might be a potential therapeutic target in combating pressure overload\u2013induced\n AF<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.118.008842","type":"journal-article","created":{"date-parts":[[2018,9,14]],"date-time":"2018-09-14T20:16:46Z","timestamp":1536956206000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Activin Receptor\u2010Like Kinase 4 Haplodeficiency Mitigates Arrhythmogenic Atrial Remodeling and Vulnerability to Atrial Fibrillation in Cardiac Pathological Hypertrophy"],"prefix":"10.1161","volume":"7","author":[{"given":"Qian","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiology Xinhua Hospital School of Medicine Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihe","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Xinhua Hospital School of Medicine Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daoliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology Xinhua Hospital School of Medicine Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwen","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Cardiology Xinhua Hospital School of Medicine Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudong","family":"Fei","sequence":"additional","affiliation":[{"name":"Department of Cardiology Xinhua Hospital School of Medicine Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuepeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Xinhua Hospital School of Medicine Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yigang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology Xinhua Hospital School of Medicine Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2010.10.029"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.06.1313"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2016.118"},{"key":"e_1_3_2_5_2","first-page":"235","article-title":"Hypertension and cardiac arrhythmias: executive summary of a consensus document from the European Heart Rhythm Association (EHRA) and ESC Council on Hypertension, endorsed by the Heart Rhythm Society (HRS), Asia\u2010Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulacion Cardiaca y Electrofisiologia (SOLEACE)","volume":"3","author":"Lip GYH","year":"2017","unstructured":"Lip GYH, Coca A, Kahan T, Boriani G, Manolis AS, Olsen MH, Oto A, Potpara TS, Steffel J, Marin F, de Oliveira Figueiredo MJ, de Simone G, Tzou WS, En Chiang C, Williams B. Hypertension and cardiac arrhythmias: executive summary of a consensus document from the European Heart Rhythm Association (EHRA) and ESC Council on Hypertension, endorsed by the Heart Rhythm Society (HRS), Asia\u2010Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulacion Cardiaca y Electrofisiologia (SOLEACE). Eur Heart J Cardiovasc Pharmacother. 2017;3:235\u2013250.","journal-title":"Eur Heart J Cardiovasc Pharmacother"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072651"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.027885"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.10.047"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-017-0634-1"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90488-C"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.16.3.1066"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a022053"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.6.844"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2010.400"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/5791510"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-2134"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2017.01.011"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.09.013"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000001020"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2017.02.002"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-016-0536-7"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.3892\/or_00001028"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.2337\/db09-1631"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvv206"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2012.06.015"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-2929-0_6"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1159\/000481642"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13105-017-0603-z"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.3390\/md15020025"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2014.06.001"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.2001.1472"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39942"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.carpath.2017.06.003"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000160367.99928.87"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2015.2"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-15-0138"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2005.10.008"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/euu294"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2014.08.021"},{"key":"e_1_3_2_40_2","first-page":"3","article-title":"Connexin 43 is involved in the sympathetic atrial fibrillation in canine and canine atrial myocytes","volume":"18","author":"Shu C","year":"2017","unstructured":"Shu C, Huang W, Zeng Z, He Y, Luo B, Liu H, Li J, Xu J. Connexin 43 is involved in the sympathetic atrial fibrillation in canine and canine atrial myocytes. Anatol J Cardiol. 2017;18:3\u20139.","journal-title":"Anatol J Cardiol"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hlc.2005.06.011"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2003.024216"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12328"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(01)01443-7"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.12659\/MSMBR.892450"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0176713"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0183671"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1177\/1470320318755269"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.02.555"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.303211"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00204-4"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-015-9615-7"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2015.11.013"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2016.07.053"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.118.008842","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:33:39Z","timestamp":1715600019000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.118.008842"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,21]]},"references-count":53,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2018,8,21]]}},"alternative-id":["10.1161\/JAHA.118.008842"],"URL":"https:\/\/doi.org\/10.1161\/jaha.118.008842","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,21]]},"assertion":[{"value":"2018-02-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e008842"}}