{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:41:29Z","timestamp":1785433289035,"version":"3.56.0"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T00:00:00Z","timestamp":1519862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL112778"],"award-info":[{"award-number":["R01 HL112778"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["P01 HL110869"],"award-info":[{"award-number":["P01 HL110869"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Moss Heart Center","award":["Not applicable"],"award-info":[{"award-number":["Not applicable"]}]},{"name":"Bashour Distinguished Chair in Physiology","award":["Not applicable"],"award-info":[{"award-number":["Not applicable"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0193769","type":"journal-article","created":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T18:48:17Z","timestamp":1519930097000},"page":"e0193769","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Genetic approaches to identify pathological limitations in aortic smooth muscle contraction"],"prefix":"10.1371","volume":"13","author":[{"given":"Jian","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanzhi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianna M.","family":"Milewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine E.","family":"Kamm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2993-7206","authenticated-orcid":true,"given":"James T.","family":"Stull","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2018,3,1]]},"reference":[{"issue":"12","key":"ref1","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1038\/ng.2007.6","article-title":"Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections","volume":"39","author":"DC Guo","year":"2007","journal-title":"Nat Genet"},{"issue":"3","key":"ref2","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/ng1721","article-title":"Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm\/aortic dissection and patent ductus arteriosus","volume":"38","author":"L Zhu","year":"2006","journal-title":"Nat Genet"},{"issue":"5","key":"ref3","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.ajhg.2010.10.006","article-title":"Mutations in myosin light chain kinase cause familial aortic dissections","volume":"87","author":"L Wang","year":"2010","journal-title":"Am J Hum Genet"},{"issue":"2","key":"ref4","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.ajhg.2013.06.019","article-title":"Recurrent gain-of-function mutation in PRKG1 causes thoracic aortic aneurysms and acute aortic dissections","volume":"93","author":"DC Guo","year":"2013","journal-title":"Am J Hum Genet"},{"issue":"1","key":"ref5","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1161\/ATVBAHA.116.303229","article-title":"Altered Smooth Muscle Cell Force Generation as a Driver of Thoracic Aortic Aneurysms and Dissections","volume":"37","author":"DM Milewicz","year":"2017","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1146\/annurev.genom.8.080706.092303","article-title":"Genetic basis of thoracic aortic aneurysms and dissections: focus on smooth muscle cell contractile dysfunction","volume":"9","author":"DM Milewicz","year":"2008","journal-title":"Annu Rev Genomics Hum Genet"},{"issue":"8","key":"ref7","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1161\/CIRCRESAHA.114.304936","article-title":"Role of mechanotransduction in vascular biology: focus on thoracic aortic aneurysms and dissections","volume":"116","author":"JD Humphrey","year":"2015","journal-title":"Circ Res"},{"issue":"5","key":"ref8","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1161\/CIRCRESAHA.110.221846","article-title":"Short Communication: Vascular Smooth Muscle Cell Stiffness As a Mechanism for Increased Aortic Stiffness With Aging","volume":"107","author":"H Qiu","year":"2010","journal-title":"Circ Res"},{"issue":"8","key":"ref9","doi-asserted-by":"crossref","first-page":"H1252","DOI":"10.1152\/ajpheart.00392.2014","article-title":"Aging impairs smooth muscle-mediated regulation of aortic stiffness: a defect in shock absorption function?","volume":"307","author":"YZ Gao","year":"2014","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"335","DOI":"10.3389\/fphys.2015.00335","article-title":"&quot;Smooth Muscle Cell Stiffness Syndrome&quot;-Revisiting the Structural Basis of Arterial Stiffness","volume":"6","author":"NL Sehgel","year":"2015","journal-title":"Front Physiol"},{"key":"ref11","first-page":"423","article-title":"Physiology of the Gastrointestinal Tract","author":"DA Hartshorne","year":"1987"},{"issue":"Pt 2","key":"ref12","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1469-7793.2000.t01-2-00177.x","article-title":"Signal transduction by G-proteins, rho-kinase and protein phosphatase to smooth muscle and non-muscle myosin II","volume":"522","author":"AP Somlyo","year":"2000","journal-title":"J Physiol"},{"issue":"Pt 21","key":"ref13","doi-asserted-by":"crossref","first-page":"5401","DOI":"10.1113\/jphysiol.2012.241315","article-title":"Size-dependent heterogeneity of contractile Ca<sup>2+<\/sup> sensitization in rat arterial smooth muscle","volume":"590","author":"T Kitazawa","year":"2012","journal-title":"J Physiol"},{"issue":"11","key":"ref14","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1161\/CIRCRESAHA.111.261743","article-title":"Rare, nonsynonymous variant in the smooth muscle-specific isoform of myosin heavy chain, MYH11, R247C, alters force generation in the aorta and phenotype of smooth muscle cells","volume":"110","author":"SQ Kuang","year":"2012","journal-title":"Circ Res"},{"issue":"11","key":"ref15","doi-asserted-by":"crossref","first-page":"7596","DOI":"10.1074\/jbc.M112.427112","article-title":"Signaling through myosin light chain kinase in smooth muscles","volume":"288","author":"N Gao","year":"2013","journal-title":"J Biol Chem"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1146\/annurev.pa.25.040185.003113","article-title":"The function of myosin and myosin light chain kinase phosphorylation in smooth muscle","volume":"25","author":"KE Kamm","year":"1985","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/372231a0","article-title":"Signal transduction and regulation in smooth muscle","volume":"372","author":"AP Somlyo","year":"1994","journal-title":"Nature"},{"issue":"2","key":"ref18","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1053\/j.gastro.2008.05.032","article-title":"Myosin light chain kinase is central to smooth muscle contraction and required for gastrointestinal motility in mice","volume":"135","author":"WQ He","year":"2008","journal-title":"Gastroenterology"},{"issue":"8","key":"ref19","doi-asserted-by":"crossref","first-page":"5522","DOI":"10.1074\/jbc.M109.062836","article-title":"Myosin light chain kinase is necessary for tonic airway smooth muscle contraction","volume":"285","author":"WC Zhang","year":"2010","journal-title":"J Biol Chem"},{"issue":"2","key":"ref20","doi-asserted-by":"crossref","first-page":"H584","DOI":"10.1152\/ajpheart.01212.2010","article-title":"Role of myosin light chain kinase in regulation of basal blood pressure and maintenance of salt-induced hypertension","volume":"301","author":"WQ He","year":"2011","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"7","key":"ref21","doi-asserted-by":"crossref","first-page":"4527","DOI":"10.1074\/jbc.R000028200","article-title":"Dedicated myosin light chain kinases with diverse cellular functions","volume":"276","author":"KE Kamm","year":"2001","journal-title":"J Biol Chem"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1152\/physrev.00023.2003","article-title":"Ca<sup>2+<\/sup>-sensitivity of smooth and non-muscle myosin II: modulation by G Proteins, kinases and myosin phosphatase","volume":"83","author":"AP Somlyo","year":"2003","journal-title":"Physiol Rev"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"6279","DOI":"10.1073\/pnas.0308742101","article-title":"Real-time evaluation of myosin light chain kinase activation in smooth muscle tissues from a transgenic calmodulin-biosensor mouse","volume":"101","author":"E Isotani","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"issue":"23","key":"ref24","doi-asserted-by":"crossref","first-page":"15541","DOI":"10.1074\/jbc.M900888200","article-title":"Signaling processes for initiating smooth muscle contraction upon neural stimulation","volume":"284","author":"HL Ding","year":"2009","journal-title":"J Biol Chem"},{"issue":"Pt 20","key":"ref25","doi-asserted-by":"crossref","first-page":"5107","DOI":"10.1113\/jphysiol.2012.235424","article-title":"Signalling to contractile proteins by muscarinic and purinergic pathways in neurally stimulated bladder smooth muscle","volume":"590","author":"MH Tsai","year":"2012","journal-title":"J Physiol"},{"issue":"6","key":"ref26","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/35014065","article-title":"Smooth-muscle contraction without smooth-muscle myosin","volume":"2","author":"I Morano","year":"2000","journal-title":"Nat Cell Biol"},{"issue":"4","key":"ref27","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1085\/jgp.200208720","article-title":"Nonmuscle myosin motor of smooth muscle","volume":"121","author":"M Lofgren","year":"2003","journal-title":"J Gen Physiol"},{"issue":"1","key":"ref28","doi-asserted-by":"crossref","first-page":"H191","DOI":"10.1152\/ajpheart.00132.2009","article-title":"Nonmuscle myosin is regulated during smooth muscle contraction","volume":"297","author":"SL Yuen","year":"2009","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"2","key":"ref29","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1124\/pr.115.010652","article-title":"Mechanisms of Vascular Smooth Muscle Contraction and the Basis for Pharmacologic Treatment of Smooth Muscle Disorders","volume":"68","author":"FV Brozovich","year":"2016","journal-title":"Pharmacol Rev"},{"issue":"1","key":"ref30","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/dvg.20448","article-title":"Efficient temporally-controlled targeted mutagenesis in smooth muscle cells of the adult mouse","volume":"47","author":"O Wendling","year":"2009","journal-title":"Genesis"},{"issue":"1","key":"ref31","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/nm1666","article-title":"G12-G13-LARG-mediated signaling in vascular smooth muscle is required for salt-induced hypertension","volume":"14","author":"A Wirth","year":"2008","journal-title":"Nat Med"},{"issue":"7","key":"ref32","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1053\/j.gastro.2013.02.045","article-title":"Altered contractile phenotypes of intestinal smooth muscle in mice deficient in myosin phosphatase target subunit 1","volume":"144","author":"WQ He","year":"2013","journal-title":"Gastroenterology"},{"issue":"Pt 14","key":"ref33","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.1113\/jphysiol.2014.273011","article-title":"Constitutive phosphorylation of myosin phosphatase targeting subunit-1 in smooth muscle","volume":"592","author":"MH Tsai","year":"2014","journal-title":"J Physiol"},{"issue":"12","key":"ref34","doi-asserted-by":"crossref","first-page":"3209","DOI":"10.1113\/JP271703","article-title":"Physiological signalling to myosin phosphatase targeting subunit-1 phosphorylation in ileal smooth muscle","volume":"594","author":"N Gao","year":"2016","journal-title":"J Physiol"},{"issue":"35","key":"ref35","doi-asserted-by":"crossref","first-page":"21223","DOI":"10.1016\/S0021-9258(19)30070-5","article-title":"Phosphorylation of smooth muscle myosin heavy and light chains. Effects of phorbol dibutyrate and agonists","volume":"264","author":"KE Kamm","year":"1989","journal-title":"J Biol Chem"},{"issue":"14","key":"ref36","doi-asserted-by":"crossref","first-page":"6293","DOI":"10.1016\/S0021-9258(19)84562-3","article-title":"Different phosphorylated forms of myosin in contracting tracheal smooth muscle","volume":"261","author":"A Persechini","year":"1986","journal-title":"J Biol Chem"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"C358","DOI":"10.1152\/ajpcell.90645.2007","article-title":"Myosin light chain kinase activation and calcium sensitization in smooth muscle <italic>in vivo<\/italic>","volume":"295","author":"Y Mizuno","year":"2008","journal-title":"Am J Physiol Cell Physiol"},{"issue":"3","key":"ref38","doi-asserted-by":"crossref","first-page":"C576","DOI":"10.1152\/ajpcell.00253.2008","article-title":"Actin cytoskeletal dynamics in smooth muscle: a new paradigm for the regulation of smooth muscle contraction","volume":"295","author":"SJ Gunst","year":"2008","journal-title":"Am J Physiol Cell Physiol"},{"issue":"2","key":"ref39","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1152\/physrev.1984.64.2.455","article-title":"Structural apparatus for force transmission in smooth muscles","volume":"64","author":"G Gabella","year":"1984","journal-title":"Physiol Rev"},{"issue":"1","key":"ref40","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.cjca.2015.11.004","article-title":"Structure of the Elastin-Contractile Units in the Thoracic Aorta and How Genes That Cause Thoracic Aortic Aneurysms and Dissections Disrupt This Structure","volume":"32","author":"A Karimi","year":"2016","journal-title":"Can J Cardiol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0193769","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T02:57:59Z","timestamp":1660532279000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0193769"}},"subtitle":[],"editor":[{"given":"Agust\u00edn","family":"Guerrero-Hernandez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2018,3,1]]},"references-count":40,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,3,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0193769","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,1]]}}}