{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:32:02Z","timestamp":1791325922732,"version":"4.3.1"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T00:00:00Z","timestamp":1664928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>Heart failure (HF) is the end stage of various cardiovascular diseases, with high morbidity and mortality, and is associated with a poor prognosis. One of the primary causes of HF is aortic valve disease, manifested by progressive aortic valve stenosis (AVS), resulting in increased left ventricular load, ventricular hypertrophy, ultimately ventricular dysfunction, and HF. Early assessment of the degree of cardiomyopathy and timely intervention is expected to improve patients\u2019 cardiac function and delay or even avoid the occurrence of HF. The Wnt signaling pathway is mainly involved in regulating myocardial insufficiency after valve stenosis. Connexin 43 protein (Cx43) is an essential target of Wnt signaling pathway that forms gap junction (GJ) structures and is widely distributed in various organs and tissues, especially in the heart. The distribution and transformation of Cx43 among cardiac cells are crucial for the development of HF. To specifically label Cx43 <jats:italic>in vivo<\/jats:italic>, we established a new <jats:italic>Cx43-BFP-GFP<\/jats:italic> mouse model with two loxp sites on both sides of the tag BFP-polyA box, which can be removed by Cre recombination. This double-reporter line endowed us with a powerful genetic tool for determining the area, spatial distribution, and functional status of Cx43. It also indicated changes in electrical conduction between cells in a steady or diseased state.<\/jats:p>","DOI":"10.3389\/fcvm.2022.1028558","type":"journal-article","created":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T05:54:40Z","timestamp":1664949280000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Expression of connexin 43 protein in cardiomyocytes of heart failure mouse model"],"prefix":"10.3389","volume":"9","author":[{"given":"Shaoyan","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzuchun","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaibin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"323","DOI":"10.5603\/KP.a2016.0183","article-title":"Hospitalisation length and prognosis in heart failure patients.","volume":"75","author":"Zaprutko","year":"2017","journal-title":"Kardiol Polska."},{"key":"B2","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1002\/ejhf.1169","article-title":"Acute heart failure: lessons learned, roads ahead.","volume":"20","author":"Ferrari","year":"2018","journal-title":"Eur J Heart Fail."},{"key":"B3","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1016\/j.carpath.2011.11.007","article-title":"The pathophysiology of heart failure.","volume":"21","author":"Kemp","year":"2012","journal-title":"Cardiovasc Pathol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1586\/14779072.4.1.25","article-title":"Aortic stenosis and the failing heart.","volume":"4","author":"Asch","year":"2006","journal-title":"Expert Rev Cardiovasc Ther."},{"key":"B5","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.jcmg.2017.01.002","article-title":"Cardiac imaging for assessing low-gradient severe aortic stenosis.","volume":"10","author":"Clavel","year":"2017","journal-title":"JACC Cardiovasc Imaging."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1093\/europace\/eut028","article-title":"Increased amount of interstitial fibrosis predicts ventricular arrhythmias, and is associated with reduced myocardial septal function in patients with obstructive hypertrophic cardiomyopathy.","volume":"15","author":"Almaas","year":"2013","journal-title":"Europace."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-019-0722-5","article-title":"Inflammation and fibrosis in murine models of heart failure.","volume":"114","author":"Bacmeister","year":"2019","journal-title":"Basic Res Cardiol."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-63336-6","article-title":"Cardiac remodeling and arrhythmogenesis are ameliorated by administration of Cx43 mimetic peptide Gap27 in heart failure rats.","volume":"10","author":"Lucero","year":"2020","journal-title":"Sci Rep."},{"key":"B9","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1007\/s00418-008-0541-5","article-title":"Characterization of the inflammatory and fibrotic response in a mouse model of cardiac pressure overload.","volume":"131","author":"Xia","year":"2009","journal-title":"Histochem Cell Biol."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-019-0497-x","article-title":"Emerging roles of gap junction proteins connexins in cancer metastasis, chemoresistance and clinical application.","volume":"26","author":"Wu","year":"2019","journal-title":"J Biomed Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/j.tcm.2006.05.002","article-title":"Connexin-mediated cardiac impulse propagation: connexin 30.2 slows atrioventricular conduction in mouse heart.","volume":"16","author":"Kreuzberg","year":"2006","journal-title":"Trends Cardiovasc Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.1161\/CIRCULATIONAHA.120.051921","article-title":"Sex-specific control of human heart maturation by the progesterone receptor.","volume":"143","author":"Sim","year":"2021","journal-title":"Circulation."},{"key":"B13","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1016\/0888-7543(91)90507-B","article-title":"The human connexin gene family of gap junction proteins: distinct chromosomal locations but similar structures.","volume":"10","author":"Fishman","year":"1991","journal-title":"Genomics."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22030987","article-title":"Importance of Cx43 for right ventricular function.","volume":"22","author":"Boengler","year":"2021","journal-title":"Int J Mol Sci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1159\/000316942","article-title":"Connexin channel-dependent signaling pathways in inflammation.","volume":"48","author":"Scheckenbach","year":"2011","journal-title":"J Vasc Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1139\/cjpp-2014-0060","article-title":"Dysregulation of Mfn2 and Drp-1 proteins in heart failure.","volume":"92","author":"Givvimani","year":"2014","journal-title":"Can J Physiol Pharmacol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1161\/CIRCEP.111.966580","article-title":"Reduced Cx43 expression triggers increased fibrosis due to enhanced fibroblast activity.","volume":"5","author":"Jansen","year":"2012","journal-title":"Circ Arrhythm Electrophysiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1016\/j.tcb.2019.07.001","article-title":"Biological Functions of Connexin43 Beyond Intercellular Communication.","volume":"29","author":"Martins-Marques","year":"2019","journal-title":"Trends Cell Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.metabol.2015.10.013","article-title":"Wnt signaling pathway in cardiac fibrosis: new insights and directions.","volume":"65","author":"Tao","year":"2016","journal-title":"Metabolism."},{"key":"B20","doi-asserted-by":"publisher","first-page":"R248","DOI":"10.1152\/ajpregu.00268.2018","article-title":"Wnt signaling regulates cytosolic translocation of connexin 43.","volume":"317","author":"Hou","year":"2019","journal-title":"Am J Physiol Regul Integr Comp Physiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1016\/j.jcmg.2016.10.007","article-title":"Myocardial fibrosis and cardiac decompensation in aortic stenosis.","volume":"10","author":"Chin","year":"2017","journal-title":"JACC Cardiovasc Imaging."},{"key":"B22","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1007\/s00441-014-2020-8","article-title":"Connexins in the heart.","volume":"360","author":"Lambiase","year":"2015","journal-title":"Cell Tissue Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1006\/jmcc.2001.1360","article-title":"Connexin37, not Cx40 and Cx43, is induced in vascular smooth muscle cells during coronary arteriogenesis.","volume":"33","author":"Cai","year":"2001","journal-title":"J Mol Cell Cardiol."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/5058313","article-title":"Transcriptome analysis of hypertrophic heart tissues from murine transverse aortic constriction and human aortic stenosis reveals key genes and transcription factors involved in cardiac remodeling induced by mechanical stress.","volume":"2019","author":"Yu","year":"2019","journal-title":"Dis Markers."},{"key":"B25","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1016\/S0735-1097(96)00563-3","article-title":"Clinical factors associated with calcific aortic valve disease. Cardiovascular health study.","volume":"29","author":"Stewart","year":"1997","journal-title":"J Am Coll Cardiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"2852","DOI":"10.1016\/j.jacc.2014.04.018","article-title":"The prevalence, incidence, progression, and risks of aortic valve sclerosis: a systematic review and meta-analysis.","volume":"63","author":"Coffey","year":"2014","journal-title":"J Am Coll Cardiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1016\/j.ijcard.2014.08.053","article-title":"The prevalence of aortic stenosis in the elderly in Iceland and predictions for the coming decades: the AGES-Reykjav\u00edk study.","volume":"176","author":"Danielsen","year":"2014","journal-title":"Int J Cardiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2796","DOI":"10.1016\/j.jacc.2021.04.014","article-title":"Moderate Aortic stenosis in patients with heart failure and reduced ejection fraction.","volume":"77","author":"Jean","year":"2021","journal-title":"J Am Coll Cardiol."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a011163","article-title":"Wnt signaling.","volume":"4","author":"Nusse","year":"2012","journal-title":"Cold Spring Harb Perspect Biol."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/srep25009","article-title":"Activation of endothelial \u03b2-catenin signaling induces heart failure.","volume":"6","author":"Nakagawa","year":"2016","journal-title":"Sci Rep."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-94169-6","article-title":"Inhibition of the canonical Wnt signaling pathway by a \u03b2-catenin\/CBP inhibitor prevents heart failure by ameliorating cardiac hypertrophy and fibrosis.","volume":"11","author":"Methatham","year":"2021","journal-title":"Sci Rep."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00840-w","article-title":"Loss of \u03b2-catenin in resident cardiac fibroblasts attenuates fibrosis induced by pressure overload in mice.","volume":"8","author":"Xiang","year":"2017","journal-title":"Nat Commun."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.546","article-title":"Cross-regulation of Connexin43 and \u03b2-catenin influences differentiation of human neural progenitor cells.","volume":"5","author":"Rinaldi","year":"2014","journal-title":"Cell Death Dis."},{"key":"B34","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1172\/JCI7798","article-title":"Wnt-1 regulation of connexin43 in cardiac myocytes.","volume":"105","author":"Ai","year":"2000","journal-title":"J Clin Invest."},{"key":"B35","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.1016\/j.bbamem.2011.07.039","article-title":"Functional consequences of abnormal Cx43 expression in the heart.","volume":"1818","author":"Fontes","year":"2012","journal-title":"Biochim Biophys Acta."},{"key":"B36","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1515\/BC.2002.076","article-title":"Structural and functional diversity of connexin genes in the mouse and human genome.","volume":"383","author":"Willecke","year":"2002","journal-title":"Biol Chem."},{"key":"B37","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.bbamem.2005.04.001","article-title":"Structural organization of gap junction channels.","volume":"1711","author":"Sosinsky","year":"2005","journal-title":"Biochim Biophys Acta."},{"key":"B38","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1016\/j.yjmcc.2006.07.017","article-title":"Cardiomyocyte-restricted deletion of connexin43 during mouse development.","volume":"41","author":"Eckardt","year":"2006","journal-title":"J Mol Cell Cardiol."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020310","article-title":"A 50% reduction of excitability but not of intercellular coupling affects conduction velocity restitution and activation delay in the mouse heart.","volume":"6","author":"Stein","year":"2011","journal-title":"PLoS One."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1161\/01.CIR.0000117402.70689.75","article-title":"Slow conduction and enhanced anisotropy increase the propensity for ventricular tachyarrhythmias in adult mice with induced deletion of connexin43.","volume":"109","author":"van Rijen","year":"2004","journal-title":"Circulation."},{"key":"B41","doi-asserted-by":"publisher","first-page":"4576","DOI":"10.1096\/fj.12-207183","article-title":"Dual reporter approaches for identification of Cre efficacy and astrocyte heterogeneity.","volume":"26","author":"Degen","year":"2012","journal-title":"FASEB J."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/1526-968X(200101)29:1<1::AID-GENE1000>3.0.CO;2-0","article-title":"Endothelium-specific replacement of the connexin43 coding region by a lacZ reporter gene.","volume":"29","author":"Theis","year":"2001","journal-title":"Genesis."}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2022.1028558\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T05:54:43Z","timestamp":1664949283000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2022.1028558\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,5]]},"references-count":42,"alternative-id":["10.3389\/fcvm.2022.1028558"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2022.1028558","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,5]]},"article-number":"1028558"}}