{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T23:47:48Z","timestamp":1784072868524,"version":"3.55.0"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T00:00:00Z","timestamp":1625702400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T00:00:00Z","timestamp":1625702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RG\/13\/19\/30568"],"award-info":[{"award-number":["RG\/13\/19\/30568"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Tissue Res"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The study of a desmoglein 2 murine model of arrhythmogenic cardiomyopathy revealed cardiac inflammation as a key early event leading to fibrosis. Arrhythmogenic cardiomyopathy (AC) is an inherited heart muscle disorder leading to ventricular arrhythmias and heart failure due to abnormalities in the cardiac desmosome. We examined how loss of desmoglein 2 (<jats:italic>Dsg2<\/jats:italic>) in the young murine heart leads to development of AC. Apoptosis was an early cellular phenotype, and RNA sequencing analysis revealed early activation of inflammatory-associated pathways in <jats:italic>Dsg2<\/jats:italic>-null (<jats:italic>Dsg2<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>) hearts at postnatal day 14 (2\u00a0weeks) that were absent in the fibrotic heart of adult mice (10\u00a0weeks). This included upregulation of iRhom2\/ADAM17 and its associated pro-inflammatory cytokines and receptors such as TNF\u03b1, IL6R and IL-6. Furthermore, genes linked to specific macrophage populations were also upregulated. This suggests cardiomyocyte stress triggers an early immune response to clear apoptotic cells allowing tissue remodelling later on in the fibrotic heart. Our analysis at the early disease stage suggests cardiac inflammation is an important response and may be one of the mechanisms responsible for AC disease progression.<\/jats:p>","DOI":"10.1007\/s00441-021-03488-7","type":"journal-article","created":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T08:03:16Z","timestamp":1625731396000},"page":"79-98","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Early inflammation precedes cardiac fibrosis and heart failure in desmoglein 2 murine model of arrhythmogenic cardiomyopathy"],"prefix":"10.1007","volume":"386","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9073-060X","authenticated-orcid":false,"given":"K. E.","family":"Ng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. J.","family":"Delaney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Thenet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Murtough","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. M.","family":"Webb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Zaman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Tsisanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Mastroianni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. L. M.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. D.","family":"Westaby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. J.","family":"Pennington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Pink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. P.","family":"Kelsell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Tinker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,8]]},"reference":[{"key":"3488_CR1","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1126\/science.1214400","volume":"335","author":"C Adrain","year":"2012","unstructured":"Adrain C, Zettl M, Christova Y, Taylor N, Freeman M (2012) Tumor necrosis factor signaling requires iRhom2 to promote trafficking and activation of TACE. Science 335:225\u2013228","journal-title":"Science"},{"key":"3488_CR2","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1172\/JCI119509","volume":"100","author":"R Agah","year":"1997","unstructured":"Agah R, Frenkel PA, French BA, Michael LH, Overbeek PA, Schneider MD (1997) Gene recombination in postmitotic cells. Targeted expression of Cre recombinase provokes cardiac-restricted, site-specific rearrangement in adult ventricular muscle in vivo. J Clin Invest 100:169\u2013179","journal-title":"J Clin Invest"},{"key":"3488_CR3","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/s41569-019-0200-7","volume":"16","author":"KM Austin","year":"2019","unstructured":"Austin KM, Trembley MA, Chandler SF, Sanders SP, Saffitz JE, Abrams DJ, Pu WT (2019) Molecular mechanisms of arrhythmogenic cardiomyopathy. Nat Rev Cardiol 16:519\u2013537","journal-title":"Nat Rev Cardiol"},{"key":"3488_CR4","doi-asserted-by":"publisher","first-page":"8912","DOI":"10.1074\/jbc.RA118.002775","volume":"293","author":"Q Aziz","year":"2018","unstructured":"Aziz Q, Finlay M, Montaigne D, Ojake L, Li Y, Anderson N, Ludwig A, Tinker A (2018) ATP-sensitive potassium channels in the sinoatrial node contribute to heart rate control and adaptation to hypoxia. J Biol Chem 293:8912\u20138921","journal-title":"J Biol Chem"},{"key":"3488_CR5","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1161\/01.CIR.94.5.983","volume":"94","author":"C Basso","year":"1996","unstructured":"Basso C, Thiene G, Corrado D, Angelini A, Nava A, Valente M (1996) Arrhythmogenic right ventricular cardiomyopathy. Dysplasia, dystrophy, or myocarditis? Circulation 94:983\u2013991","journal-title":"Circulation"},{"key":"3488_CR6","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1161\/CIRCULATIONAHA.119.043931","volume":"141","author":"ALP Caforio","year":"2020","unstructured":"Caforio ALP, Re F, Avella A, Marcolongo R, Baratta P, Seguso M, Gallo N, Plebani M, Izquierdo-Bajo A, Cheng CY, Syrris P, Elliott PM, d\u2019Amati G, Thiene G, Basso C, Gregori D, Iliceto S, Zachara E (2020) Evidence from family studies for autoimmunity in arrhythmogenic right ventricular cardiomyopathy: associations of circulating anti-heart and anti-intercalated disk autoantibodies with disease severity and family history. Circulation 141:1238\u20131248","journal-title":"Circulation"},{"key":"3488_CR7","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1136\/jcp.53.5.382","volume":"53","author":"F Calabrese","year":"2000","unstructured":"Calabrese F, Angelini A, Thiene G, Basso C, Nava A, Valente M (2000) No detection of enteroviral genome in the myocardium of patients with arrhythmogenic right ventricular cardiomyopathy. J Clin Pathol 53:382\u2013387","journal-title":"J Clin Pathol"},{"key":"3488_CR8","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.carpath.2005.10.004","volume":"15","author":"F Calabrese","year":"2006","unstructured":"Calabrese F, Basso C, Carturan E, Valente M, Thiene G (2006) Arrhythmogenic right ventricular cardiomyopathy\/dysplasia: is there a role for viruses? Cardiovasc Pathol 15:11\u201317","journal-title":"Cardiovasc Pathol"},{"key":"3488_CR9","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1136\/jclinpath-2012-201022","volume":"65","author":"O Campuzano","year":"2012","unstructured":"Campuzano O, Alcalde M, Iglesias A, Barahona-Dussault C, Sarquella-Brugada G, Benito B, Arzamendi D, Flores J, Leung TK, Talajic M, Oliva A, Brugada R (2012) Arrhythmogenic right ventricular cardiomyopathy: severe structural alterations are associated with inflammation. J Clin Pathol 65:1077\u20131083","journal-title":"J Clin Pathol"},{"key":"3488_CR10","doi-asserted-by":"publisher","first-page":"3932","DOI":"10.1093\/eurheartj\/ehy567","volume":"39","author":"D Chatterjee","year":"2018","unstructured":"Chatterjee D, Fatah M, Akdis D, Spears DA, Koopmann TT, Mittal K, Rafiq MA, Cattanach BM, Zhao Q, Healey JS, Ackerman MJ, Bos JM, Sun Y, Maynes JT, Brunckhorst C, Medeiros-Domingo A, Duru F, Saguner AM, Hamilton RM (2018) An autoantibody identifies arrhythmogenic right ventricular cardiomyopathy and participates in its pathogenesis. Eur Heart J 39:3932\u20133944","journal-title":"Eur Heart J"},{"key":"3488_CR11","first-page":"263","volume":"6","author":"L Ch\u00e1vez-Gal\u00e1n","year":"2015","unstructured":"Ch\u00e1vez-Gal\u00e1n L, Olleros ML, Vesin D, Garcia I (2015) Much more than M1 and M2 macrophages, there are also CD169(+) and TCR(+) macrophages. Front Immunol 6:263","journal-title":"Front Immunol"},{"key":"3488_CR12","doi-asserted-by":"crossref","unstructured":"Chelko SP, Asimaki A, Andersen P, Bedja D, Amat-Alarcon N, DeMazumder D, Jasti R, MacRae CA, Leber R, Kleber AG, Saffitz JE, Judge DP (2016) Central role for GSK3\u03b2 in the pathogenesis of arrhythmogenic cardiomyopathy. JCI Insight 1","DOI":"10.1172\/jci.insight.85923"},{"key":"3488_CR13","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1161\/CIRCULATIONAHA.119.040676","volume":"140","author":"SP Chelko","year":"2019","unstructured":"Chelko SP, Asimaki A, Lowenthal J, Bueno-Beti C, Bedja D, Scalco A, Amat-Alarcon N, Andersen P, Judge DP, Tung L, Saffitz JE (2019) Therapeutic modulation of the immune response in arrhythmogenic cardiomyopathy. Circulation 140:1491\u20131505","journal-title":"Circulation"},{"key":"3488_CR14","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1016\/j.yjmcc.2010.10.033","volume":"51","author":"M Dobaczewski","year":"2011","unstructured":"Dobaczewski M, Chen W, Frangogiannis NG (2011) Transforming growth factor (TGF)-\u03b2 signaling in cardiac remodeling. J Mol Cell Cardiol 51:600\u2013606","journal-title":"J Mol Cell Cardiol"},{"key":"3488_CR15","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1093\/nar\/30.1.207","volume":"30","author":"R Edgar","year":"2002","unstructured":"Edgar R, Domrachev M, Lash AE (2002) Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res 30:207\u2013210","journal-title":"Nucleic Acids Res"},{"key":"3488_CR16","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1078\/0171-9335-00278","volume":"81","author":"L Eshkind","year":"2002","unstructured":"Eshkind L, Tian Q, Schmidt A, Franke WW, Windoffer R, Leube RE (2002) Loss of desmoglein 2 suggests essential functions for early embryonic development and proliferation of embryonal stem cells. Eur J Cell Biol 81:592\u2013598","journal-title":"Eur J Cell Biol"},{"key":"3488_CR17","doi-asserted-by":"publisher","first-page":"C576","DOI":"10.1152\/ajpcell.00028.2019","volume":"317","author":"M Finlay","year":"2019","unstructured":"Finlay M, Bhar-Amato J, Ng KE, Santos D, Orini M, Vyas V, Taggart P, Grace AA, Huang CL, Lambiase PD, Tinker A (2019) Autonomic modulation of the electrical substrate in mice haploinsufficient for cardiac sodium channels: a model of the Brugada syndrome. Am J Physiol Cell Physiol 317:C576\u2013C583","journal-title":"Am J Physiol Cell Physiol"},{"key":"3488_CR18","doi-asserted-by":"publisher","first-page":"2523","DOI":"10.1152\/physrev.00068.2017","volume":"98","author":"V Frodermann","year":"2018","unstructured":"Frodermann V, Nahrendorf M (2018) Macrophages and cardiovascular health. Physiol Rev 98:2523\u20132569","journal-title":"Physiol Rev"},{"key":"3488_CR19","doi-asserted-by":"publisher","first-page":"2012","DOI":"10.1172\/JCI27751","volume":"116","author":"E Garcia-Gras","year":"2006","unstructured":"Garcia-Gras E, Lombardi R, Giocondo MJ, Willerson JT, Schneider MD, Khoury DS, Marian AJ (2006) Suppression of canonical Wnt\/beta-catenin signaling by nuclear plakoglobin recapitulates phenotype of arrhythmogenic right ventricular cardiomyopathy. J Clin Invest 116:2012\u20132021","journal-title":"J Clin Invest"},{"key":"3488_CR20","doi-asserted-by":"publisher","first-page":"1942","DOI":"10.1093\/eurheartj\/ehr472","volume":"33","author":"J Gomes","year":"2012","unstructured":"Gomes J, Finlay M, Ahmed AK, Ciaccio EJ, Asimaki A, Saffitz JE, Quarta G, Nobles M, Syrris P, Chaubey S, McKenna WJ, Tinker A, Lambiase PD (2012) Electrophysiological abnormalities precede overt structural changes in arrhythmogenic right ventricular cardiomyopathy due to mutations in desmoplakin-A combined murine and human study. Eur Heart J 33:1942\u20131953","journal-title":"Eur Heart J"},{"key":"3488_CR21","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1161\/CIRCRESAHA.115.303567","volume":"115","author":"T Heidt","year":"2014","unstructured":"Heidt T, Courties G, Dutta P, Sager HB, Sebas M, Iwamoto Y, Sun Y, Da Silva N, Panizzi P, van der Laan AM, van der Lahn AM, Swirski FK, Weissleder R, Nahrendorf M (2014) Differential contribution of monocytes to heart macrophages in steady-state and after myocardial infarction. Circ Res 115:284\u2013295","journal-title":"Circ Res"},{"key":"3488_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/nar\/gkn923","volume":"37","author":"Huang dW, Sherman BT, Lempicki RA,","year":"2009","unstructured":"Huang dW, Sherman BT, Lempicki RA, (2009a) Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37:1\u201313","journal-title":"Nucleic Acids Res"},{"key":"3488_CR23","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nprot.2008.211","volume":"4","author":"Huang dW, Sherman BT, Lempicki RA,","year":"2009","unstructured":"Huang dW, Sherman BT, Lempicki RA, (2009b) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44\u201357","journal-title":"Nat Protoc"},{"key":"3488_CR24","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1016\/j.cell.2017.03.050","volume":"169","author":"M Hulsmans","year":"2017","unstructured":"Hulsmans M, Clauss S, Xiao L, Aguirre AD, King KR, Hanley A, Hucker WJ, W\u00fclfers EM, Seemann G, Courties G, Iwamoto Y, Sun Y, Savol AJ, Sager HB, Lavine KJ, Fishbein GA, Capen DE, Da Silva N, Miquerol L, Wakimoto H, Seidman CE, Seidman JG, Sadreyev RI, Naxerova K, Mitchell RN, Brown D, Libby P, Weissleder R, Swirski FK, Kohl P, Vinegoni C, Milan DJ, Ellinor PT, Nahrendorf M (2017) Macrophages facilitate electrical conduction in the heart. Cell 169:510-522.e520","journal-title":"Cell"},{"key":"3488_CR25","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1161\/CIRCGENETICS.114.000974","volume":"8","author":"S Kant","year":"2015","unstructured":"Kant S, Holth\u00f6fer B, Magin TM, Krusche CA, Leube RE (2015) Desmoglein 2-dependent arrhythmogenic cardiomyopathy is caused by a loss of adhesive function. Circ Cardiovasc Genet 8:553\u2013563","journal-title":"Circ Cardiovasc Genet"},{"key":"3488_CR26","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1517\/14728222.2013.744823","volume":"17","author":"H Koga","year":"2013","unstructured":"Koga H, Tsuruta D, Ohyama B, Ishii N, Hamada T, Ohata C, Furumura M, Hashimoto T (2013) Desmoglein 3, its pathogenecity and a possibility for therapeutic target in pemphigus vulgaris. Expert Opin Ther Targets 17:293\u2013306","journal-title":"Expert Opin Ther Targets"},{"key":"3488_CR27","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/B978-0-12-394311-8.00005-4","volume":"116","author":"AP Kowalczyk","year":"2013","unstructured":"Kowalczyk AP, Green KJ (2013) Structure, function, and regulation of desmosomes. Prog Mol Biol Transl Sci 116:95\u2013118","journal-title":"Prog Mol Biol Transl Sci"},{"key":"3488_CR28","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1007\/s00395-011-0175-y","volume":"106","author":"CA Krusche","year":"2011","unstructured":"Krusche CA, Holth\u00f6fer B, Hofe V, van de Sandt AM, Eshkind L, Bockamp E, Merx MW, Kant S, Windoffer R, Leube RE (2011) Desmoglein 2 mutant mice develop cardiac fibrosis and dilation. Basic Res Cardiol 106:617\u2013633","journal-title":"Basic Res Cardiol"},{"key":"3488_CR29","doi-asserted-by":"publisher","first-page":"520","DOI":"10.7150\/ijbs.8879","volume":"10","author":"YC Liu","year":"2014","unstructured":"Liu YC, Zou XB, Chai YF, Yao YM (2014) Macrophage polarization in inflammatory diseases. Int J Biol Sci 10:520\u2013529","journal-title":"Int J Biol Sci"},{"key":"3488_CR30","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/s41584-019-0259-x","volume":"15","author":"R L\u00f3pez-Mej\u00edas","year":"2019","unstructured":"L\u00f3pez-Mej\u00edas R, Gonz\u00e1lez-Gay MA (2019) IL-6: linking chronic inflammation and vascular calcification. Nat Rev Rheumatol 15:457\u2013459","journal-title":"Nat Rev Rheumatol"},{"key":"3488_CR31","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1007\/s00395-020-0803-5","volume":"115","author":"N Lubos","year":"2020","unstructured":"Lubos N, van der Gaag S, Ger\u00e7ek M, Kant S, Leube RE, Krusche CA (2020) Inflammation shapes pathogenesis of murine arrhythmogenic cardiomyopathy. Basic Res Cardiol 115:42","journal-title":"Basic Res Cardiol"},{"key":"3488_CR32","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.ijcard.2018.05.116","volume":"271","author":"D Martins","year":"2018","unstructured":"Martins D, Ovaert C, Khraiche D, Boddaert N, Bonnet D, Raimondi F (2018) Myocardial inflammation detected by cardiac MRI in arrhythmogenic right ventricular cardiomyopathy: a paediatric case series. Int J Cardiol 271:81\u201386","journal-title":"Int J Cardiol"},{"key":"3488_CR33","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1126\/science.1214448","volume":"335","author":"DR McIlwain","year":"2012","unstructured":"McIlwain DR, Lang PA, Maretzky T, Hamada K, Ohishi K, Maney SK, Berger T, Murthy A, Duncan G, Xu HC, Lang KS, H\u00e4ussinger D, Wakeham A, Itie-Youten A, Khokha R, Ohashi PS, Blobel CP, Mak TW (2012) iRhom2 regulation of TACE controls TNF-mediated protection against Listeria and responses to LPS. Science 335:229\u2013232","journal-title":"Science"},{"key":"3488_CR34","doi-asserted-by":"publisher","first-page":"2119","DOI":"10.1016\/S0140-6736(00)02379-5","volume":"355","author":"G McKoy","year":"2000","unstructured":"McKoy G, Protonotarios N, Crosby A, Tsatsopoulou A, Anastasakis A, Coonar A, Norman M, Baboonian C, Jeffery S, McKenna WJ (2000) Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease). Lancet 355:2119\u20132124","journal-title":"Lancet"},{"key":"3488_CR35","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1038\/nri2448","volume":"8","author":"DM Mosser","year":"2008","unstructured":"Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8:958\u2013969","journal-title":"Nat Rev Immunol"},{"key":"3488_CR36","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1038\/s41591-018-0064-0","volume":"24","author":"M Nahrendorf","year":"2018","unstructured":"Nahrendorf M (2018) Myeloid cell contributions to cardiovascular health and disease. Nat Med 24:711\u2013720","journal-title":"Nat Med"},{"key":"3488_CR37","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1161\/CIRCRESAHA.116.309194","volume":"119","author":"M Nahrendorf","year":"2016","unstructured":"Nahrendorf M, Swirski FK (2016) Abandoning M1\/M2 for a network model of macrophage function. Circ Res 119:414\u2013417","journal-title":"Circ Res"},{"key":"3488_CR38","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/S1054-8807(99)00007-1","volume":"8","author":"T Nishikawa","year":"1999","unstructured":"Nishikawa T, Ishiyama S, Nagata M, Sakomura Y, Nakazawa M, Momma K, Hiroe M, Kasajima T (1999) Programmed cell death in the myocardium of arrhythmogenic right ventricular cardiomyopathy in children and adults. Cardiovasc Pathol 8:185\u2013189","journal-title":"Cardiovasc Pathol"},{"key":"3488_CR39","doi-asserted-by":"publisher","first-page":"2761","DOI":"10.1093\/hmg\/9.18.2761","volume":"9","author":"EE Norgett","year":"2000","unstructured":"Norgett EE, Hatsell SJ, Carvajal-Huerta L, Cabezas JC, Common J, Purkis PE, Whittock N, Leigh IM, Stevens HP, Kelsell DP (2000) Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma. Hum Mol Genet 9:2761\u20132766","journal-title":"Hum Mol Genet"},{"key":"3488_CR40","doi-asserted-by":"publisher","first-page":"e26","DOI":"10.1016\/j.ijcard.2011.09.017","volume":"157","author":"AP Patrianakos","year":"2012","unstructured":"Patrianakos AP, Protonotarios N, Nyktari E, Pagonidis K, Tsatsopoulou A, Parthenakis FI, Vardas PE (2012) Arrhythmogenic right ventricular cardiomyopathy\/dysplasia and troponin release. Myocarditis or the \u201chot phase\u201d of the disease? Int J Cardiol 157:e26-28","journal-title":"Int J Cardiol"},{"key":"3488_CR41","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1161\/CIRCULATIONAHA.105.583674","volume":"113","author":"K Pilichou","year":"2006","unstructured":"Pilichou K, Nava A, Basso C, Beffagna G, Bauce B, Lorenzon A, Frigo G, Vettori A, Valente M, Towbin J, Thiene G, Danieli GA, Rampazzo A (2006) Mutations in desmoglein-2 gene are associated with arrhythmogenic right ventricular cardiomyopathy. Circulation 113:1171\u20131179","journal-title":"Circulation"},{"key":"3488_CR42","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1084\/jem.20090641","volume":"206","author":"K Pilichou","year":"2009","unstructured":"Pilichou K, Remme CA, Basso C, Campian ME, Rizzo S, Barnett P, Scicluna BP, Bauce B, van den Hoff MJ, de Bakker JM, Tan HL, Valente M, Nava A, Wilde AA, Moorman AF, Thiene G, Bezzina CR (2009) Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2-related arrhythmogenic right ventricular cardiomyopathy. J Exp Med 206:1787\u20131802","journal-title":"J Exp Med"},{"key":"3488_CR43","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1189\/jlb.71.4.597","volume":"71","author":"G Raes","year":"2002","unstructured":"Raes G, De Baetselier P, No\u00ebl W, Beschin A, Brombacher F, Hassanzadeh GhG (2002) Differential expression of FIZZ1 and Ym1 in alternatively versus classically activated macrophages. J Leukoc Biol 71:597\u2013602","journal-title":"J Leukoc Biol"},{"key":"3488_CR44","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1093\/cvr\/cvs219","volume":"95","author":"S Rizzo","year":"2012","unstructured":"Rizzo S, Lodder EM, Verkerk AO, Wolswinkel R, Beekman L, Pilichou K, Basso C, Remme CA, Thiene G, Bezzina CR (2012) Intercalated disc abnormalities, reduced Na(+) current density, and conduction slowing in desmoglein-2 mutant mice prior to cardiomyopathic changes. Cardiovasc Res 95:409\u2013418","journal-title":"Cardiovasc Res"},{"key":"3488_CR45","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1146\/annurev.med.052208.130419","volume":"61","author":"S Sen-Chowdhry","year":"2010","unstructured":"Sen-Chowdhry S, Morgan RD, Chambers JC, McKenna WJ (2010) Arrhythmogenic cardiomyopathy: etiology, diagnosis, and treatment. Annu Rev Med 61:233\u2013253","journal-title":"Annu Rev Med"},{"key":"3488_CR46","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1038\/s41577-018-0065-8","volume":"18","author":"FK Swirski","year":"2018","unstructured":"Swirski FK, Nahrendorf M (2018) Cardioimmunology: the immune system in cardiac homeostasis and disease. Nat Rev Immunol 18:733\u2013744","journal-title":"Nat Rev Immunol"},{"key":"3488_CR47","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1093\/eurheartj\/ehl380","volume":"28","author":"P Syrris","year":"2007","unstructured":"Syrris P, Ward D, Asimaki A, Evans A, Sen-Chowdhry S, Hughes SE, McKenna WJ (2007) Desmoglein-2 mutations in arrhythmogenic right ventricular cardiomyopathy: a genotype-phenotype characterization of familial disease. Eur Heart J 28:581\u2013588","journal-title":"Eur Heart J"},{"key":"3488_CR48","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1161\/CIRCULATIONAHA.105.561654","volume":"113","author":"P Syrris","year":"2006","unstructured":"Syrris P, Ward D, Asimaki A, Sen-Chowdhry S, Ebrahim HY, Evans A, Hitomi N, Norman M, Pantazis A, Shaw AL, Elliott PM, McKenna WJ (2006a) Clinical expression of plakophilin-2 mutations in familial arrhythmogenic right ventricular cardiomyopathy. Circulation 113:356\u2013364","journal-title":"Circulation"},{"key":"3488_CR49","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1086\/509122","volume":"79","author":"P Syrris","year":"2006","unstructured":"Syrris P, Ward D, Evans A, Asimaki A, Gandjbakhch E, Sen-Chowdhry S, McKenna WJ (2006b) Arrhythmogenic right ventricular dysplasia\/cardiomyopathy associated with mutations in the desmosomal gene desmocollin-2. Am J Hum Genet 79:978\u2013984","journal-title":"Am J Hum Genet"},{"key":"3488_CR50","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1093\/cvr\/cvw259","volume":"113","author":"SH Vermij","year":"2017","unstructured":"Vermij SH, Abriel H, van Veen TA (2017) Refining the molecular organization of the cardiac intercalated disc. Cardiovasc Res 113:259\u2013275","journal-title":"Cardiovasc Res"}],"container-title":["Cell and Tissue Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00441-021-03488-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00441-021-03488-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00441-021-03488-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,5]],"date-time":"2023-02-05T00:05:35Z","timestamp":1675555535000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00441-021-03488-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,8]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["3488"],"URL":"https:\/\/doi.org\/10.1007\/s00441-021-03488-7","relation":{},"ISSN":["0302-766X","1432-0878"],"issn-type":[{"value":"0302-766X","type":"print"},{"value":"1432-0878","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,8]]},"assertion":[{"value":"8 September 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animals were cared for according to the Animals (Scientific Procedures) Act 1986. Mice were maintained in an animal core facility under UK Home Office guidelines related to animal welfare at Charterhouse Campus, Queen Mary University of London.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}