{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T12:22:08Z","timestamp":1788956528570,"version":"build-2803163510"},"reference-count":30,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T00:00:00Z","timestamp":1613606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100016168","name":"Ludwig Boltzmann Gesellschaft","doi-asserted-by":"publisher","award":["REM 2017-2020, 2021-2024"],"award-info":[{"award-number":["REM 2017-2020, 2021-2024"]}],"id":[{"id":"10.13039\/501100016168","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Tenascin-C (TN-C) plays a maladaptive role in left ventricular (LV) hypertrophy following pressure overload. However, the role of TN-C in LV regression following mechanical unloading is unknown. Methods: LV hypertrophy was induced by transverse aortic constriction for 10 weeks followed by debanding for 2 weeks in wild type (Wt) and TN-C knockout (TN-C KO) mice. Cardiac function was assessed by serial magnetic resonance imaging. The expression of fibrotic markers and drivers (angiotensin-converting enzyme-1, ACE-1) was determined in LV tissue as well as human cardiac fibroblasts (HCFs) after TN-C treatment. Results: Chronic pressure overload resulted in a significant decline in cardiac function associated with LV dilation as well as upregulation of TN-C, collagen 1 (Col 1), and ACE-1 in Wt as compared to TN-C KO mice. Reverse remodeling in Wt mice partially improved cardiac function and fibrotic marker expression; however, TN-C protein expression remained unchanged. In HCF, TN-C strongly induced the upregulation of ACE 1 and Col 1. Conclusions: Pressure overload, when lasting long enough to induce HF, has less potential for reverse remodeling in mice. This may be due to significant upregulation of TN-C expression, which stimulates ACE 1, Col 1, and alpha-smooth muscle actin (\u03b1-SMA) upregulation in fibroblasts. Consequently, addressing TN-C in LV hypertrophy might open a new window for future therapeutics.<\/jats:p>","DOI":"10.3390\/ijms22042023","type":"journal-article","created":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T20:56:21Z","timestamp":1613681781000},"page":"2023","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The Role of Tenascin C in Cardiac Reverse Remodeling Following Banding\u2013Debanding of the Ascending Aorta"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1033-295X","authenticated-orcid":false,"given":"Mireia","family":"Perera-Gonzalez","sequence":"first","affiliation":[{"name":"Ludwig Boltzmann Institute for Cardiovascular Research at the Center for Biomedical Research, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Bioengineering and Aerospace Engineering Department, Carlos III University of Madrid, 28911 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4652-1998","authenticated-orcid":false,"given":"Attila","family":"Kiss","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Cardiovascular Research at the Center for Biomedical Research, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Kaiser","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Cardiovascular Research at the Center for Biomedical Research, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Holzweber","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Cardiovascular Research at the Center for Biomedical Research, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Nagel","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Cardiovascular Research at the Center for Biomedical Research, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Cardiac Surgery, University Hospital St. Poelten, 3100 St. Poelten, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Watzinger","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Cardiovascular Research at the Center for Biomedical Research, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0599-6893","authenticated-orcid":false,"given":"Eylem","family":"Acar","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Cardiovascular Research at the Center for Biomedical Research, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra Lujza","family":"Szabo","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Cardiovascular Research at the Center for Biomedical Research, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8593-4360","authenticated-orcid":false,"given":"In\u00eas Fonseca","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Cardiovascular Research at the Center for Biomedical Research, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Weber","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Cardiovascular Research at the Center for Biomedical Research, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick Michael","family":"Pilz","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Cardiovascular Research at the Center for Biomedical Research, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubos","family":"Budinsky","sequence":"additional","affiliation":[{"name":"Preclinical Imaging Lab at the Center of Biomedical Research, Department of Radiology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3169-778X","authenticated-orcid":false,"given":"Thomas","family":"Helbich","sequence":"additional","affiliation":[{"name":"Preclinical Imaging Lab at the Center of Biomedical Research, Department of Radiology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4641-7202","authenticated-orcid":false,"given":"Bruno Karl","family":"Podesser","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Cardiovascular Research at the Center for Biomedical Research, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Cardiac Surgery, University Hospital St. Poelten, 3100 St. Poelten, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1172\/JCI108079","article-title":"Wall stress and patterns of hypertrophy in the human left ventricle","volume":"56","author":"Grossman","year":"1975","journal-title":"J. Clin. Investig."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1161\/01.CIR.79.4.744","article-title":"Left-Ventricular Myocardial Structure in Aortic-Valve Disease before, Intermediate, and Late after Aortic-Valve Replacement","volume":"79","author":"Krayenbuehl","year":"1989","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1161\/CIRCULATIONAHA.112.000029","article-title":"Mechanically unloading the left ventricle before coronary reperfusion reduces left ventricular wall stress and myocardial infarct size","volume":"128","author":"Kapur","year":"2013","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1161\/01.CIR.91.11.2717","article-title":"Reversal of chronic ventricular dilation in patients with end-stage cardiomyopathy by prolonged mechanical unloading","volume":"91","author":"Levin","year":"1995","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/nrcardio.2017.139","article-title":"Reverse remodelling and myocardial recovery in heart failure","volume":"15","author":"Kim","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kassner, A., Oezpeker, C., Gummert, J., Zittermann, A., Gartner, A., Tiesmeier, J., Fox, H., Morshuis, M., and Milting, H. (2020). Mechanical circulatory support does not reduce advanced myocardial fibrosis in patients with end-stage heart failure. Eur. J. Heart Fail.","DOI":"10.1002\/ejhf.2021"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/j.1748-1716.2011.02369.x","article-title":"A mouse model of reverse cardiac remodelling following banding-debanding of the ascending aorta","volume":"205","author":"Bjornstad","year":"2012","journal-title":"Acta Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.1253\/circj.CJ-12-1033","article-title":"Tenascin-C in cardiovascular tissue remodeling: From development to inflammation and repair","volume":"76","year":"2012","journal-title":"Circ. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/0955-0674(93)90037-Q","article-title":"Tenascin-C, tenascin-R and tenascin-X: A family of talented proteins in search of functions","volume":"5","author":"Erickson","year":"1993","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1097\/HJH.0000000000001628","article-title":"Tenascin-C promotes chronic pressure overload-induced cardiac dysfunction, hypertrophy and myocardial fibrosis","volume":"36","author":"Podesser","year":"2018","journal-title":"J. Hypertens"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1002\/ehf2.12794","article-title":"Tenascin-C aggravates ventricular dilatation and angiotensin-converting enzyme activity after myocardial infarction in mice","volume":"7","author":"Santer","year":"2020","journal-title":"ESC Heart Fail."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4107587","DOI":"10.1155\/2017\/6490349","article-title":"Preservation of Myocardial Perfusion and Function by Keeping Hypertrophied Heart Empty and Beating for Valve Surgery: An In Vivo MR Study of Pig Hearts","volume":"2017","author":"Wang","year":"2017","journal-title":"Biomed. Res. Int."},{"key":"ref_13","first-page":"1237","article-title":"Tenascin-C promotes healing of Habu-snake venom-induced glomerulonephritis: Studies in knockout congenic mice and in culture","volume":"152","author":"Nakao","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_14","first-page":"1071","article-title":"Corneal wound healing in tenascin knockout mouse","volume":"40","author":"Matsuda","year":"1999","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1046\/j.1523-1747.1998.00401.x","article-title":"Effect of tenascin-C deficiency on chemically induced dermatitis in the mouse","volume":"111","author":"Koyama","year":"1998","journal-title":"J. Investig. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Heiberg, E., Wigstrom, L., Carlsson, M., Bolger, A.F., and Karlsson, M. (2005). Time Resolved Three-Dimensional Automated Segmentation of the Left Ventricle, IEEE. Computers in Cardiology.","DOI":"10.1109\/CIC.2005.1588172"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1038\/nprot.2006.306","article-title":"A continuous fluorescence resonance energy transfer angiotensin I-converting enzyme assay","volume":"1","author":"Carmona","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Fagyas, M., Uri, K., Siket, I.M., Fulop, G.A., Csato, V., Darago, A., Boczan, J., Banyai, E., Szentkiralyi, I.E., and Maros, T.M. (2014). New perspectives in the renin-angiotensin-aldosterone system (RAAS) II: Albumin suppresses angiotensin converting enzyme (ACE) activity in human. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087844"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1097\/HJH.0000000000002097","article-title":"Epigenetic modulation of tenascin C in the heart: Implications on myocardial ischemia, hypertrophy and metabolism","volume":"37","author":"Goncalves","year":"2019","journal-title":"J. Hypertens."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.jtcvs.2017.09.133","article-title":"One-year outcomes after rapid-deployment aortic valve replacement","volume":"155","author":"Young","year":"2018","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1093\/ejcts\/ezx103","article-title":"Long-term outcomes of a rapid deployment aortic valve: Data up to 5 years","volume":"52","author":"Laufer","year":"2017","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.amjcard.2017.11.013","article-title":"Relation Between Renin-Angiotensin System Blockers and Survival Following Isolated Aortic Valve Replacement for Aortic Stenosis","volume":"121","author":"Magne","year":"2018","journal-title":"Am. J. Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.ajpath.2014.11.027","article-title":"Nonclassical resident macrophages are important determinants in the development of myocardial fibrosis","volume":"185","author":"Falkenham","year":"2015","journal-title":"Am. J. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ma, F., Li, Y., Jia, L., Han, Y., Cheng, J., Li, H., Qi, Y., and Du, J. (2012). Macrophage-stimulated cardiac fibroblast production of IL-6 is essential for TGF beta\/Smad activation and cardiac fibrosis induced by angiotensin II. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035144"},{"key":"ref_25","first-page":"24","article-title":"Multiscale Analysis of Extracellular Matrix Remodeling in the Failing Heart","volume":"128","author":"Silva","year":"2020","journal-title":"Circ. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/ejhf.464","article-title":"Significance of myocardial tenascin-C expression in left ventricular remodelling and long-term outcome in patients with dilated cardiomyopathy","volume":"18","author":"Yokokawa","year":"2016","journal-title":"Eur. J. Heart Fail."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.hlc.2012.10.005","article-title":"Prognostic values of serum tenascin-C in patients with ischaemic heart disease and heart failure","volume":"22","author":"Yao","year":"2013","journal-title":"Heart Lung Circ."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"31","DOI":"10.5551\/jat.42887","article-title":"Tenascin C: A Potential Biomarker for Predicting the Severity of Coronary Atherosclerosis","volume":"26","author":"Gao","year":"2019","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1016\/j.jacc.2006.03.033","article-title":"Serum tenascin-C might be a novel predictor of left ventricular remodeling and prognosis after acute myocardial infarction","volume":"47","author":"Sato","year":"2006","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.cardfail.2012.02.009","article-title":"Prognostic value of serum tenascin-C levels on long-term outcome after acute myocardial infarction","volume":"18","author":"Sato","year":"2012","journal-title":"J. Card Fail."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/4\/2023\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:25:52Z","timestamp":1760160352000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/4\/2023"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,18]]},"references-count":30,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["ijms22042023"],"URL":"https:\/\/doi.org\/10.3390\/ijms22042023","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,18]]}}}