{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:50:13Z","timestamp":1792785013382,"version":"4.5.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T00:00:00Z","timestamp":1641513600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T00:00:00Z","timestamp":1641513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"the Setsuro Fujii Memorial, Osaka Foundation for the Promotion of Fundamental Medical Research"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Suture-based transverse aortic constriction (TAC) in mice is one of the most frequently used experimental models for cardiac pressure overload-induced heart failure. However, the incidence of heart failure in the conventional TAC depends on the operator\u2019s skill. To optimize and simplify this method, we proposed O-ring-induced transverse aortic constriction (OTAC) in mice. C57BL\/6J mice were subjected to OTAC, in which an o-ring was applied to the transverse aorta (between the brachiocephalic artery and the left common carotid artery) and tied with a triple knot. We used different inner diameters of o-rings were 0.50 and 0.45\u00a0mm. Pressure overload by OTAC promoted left ventricular (LV) hypertrophy. OTAC also increased lung weight, indicating severe pulmonary congestion. Echocardiographic findings revealed that both OTAC groups developed LV hypertrophy within one week after the procedure and gradually reduced LV fractional shortening. In addition, significant elevations in gene expression related to heart failure, LV hypertrophy, and LV fibrosis were observed in the LV of OTAC mice. We demonstrated the OTAC method, which is a simple and effective cardiac pressure overload method in mice. This method will efficiently help us understand heart failure (HF) mechanisms with reduced LV ejection fraction (HFrEF) and cardiac hypertrophy.<\/jats:p>","DOI":"10.1038\/s41598-021-04096-9","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T06:03:34Z","timestamp":1641535414000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["O-ring-induced transverse aortic constriction (OTAC) is a new simple method to develop cardiac hypertrophy and heart failure in mice"],"prefix":"10.1038","volume":"12","author":[{"given":"Yasuhisa","family":"Nakao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Aono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Hamaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayo","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohisa","family":"Sakaue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuji","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuntaro","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Yamaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,7]]},"reference":[{"key":"4096_CR1","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.pcad.2006.02.001","volume":"48","author":"AH Gradman","year":"2006","unstructured":"Gradman, A. H. & Alfayoumi, F. From left ventricular hypertrophy to congestive heart failure: Management of hypertensive heart disease. Prog. Cardiovasc. Dis. 48, 326\u2013341 (2006).","journal-title":"Prog. Cardiovasc. Dis."},{"key":"4096_CR2","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1093\/eurheartj\/ehw128","volume":"37","author":"P Ponikowski","year":"2016","unstructured":"Ponikowski, P. et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur. J. Heart Fail. 37, 2129\u20132200 (2016).","journal-title":"Eur. J. Heart Fail."},{"key":"4096_CR3","doi-asserted-by":"publisher","first-page":"2084","DOI":"10.1253\/circj.CJ-19-0342","volume":"83","author":"H Tsutsui","year":"2019","unstructured":"Tsutsui, H. et al. JCS 2017\/JHFS 2017 guideline on diagnosis and treatment of acute and chronic heart failure\u2014 Digest version. Circ. J. 83, 2084\u20132184 (2019).","journal-title":"Circ. J."},{"key":"4096_CR4","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1161\/01.RES.75.3.401","volume":"75","author":"W Luo","year":"1994","unstructured":"Luo, W. et al. Targeted ablation of the phospholamban gene is associated with markedly enhanced myocardial contractility and loss of beta-agonist stimulation. Circ. Res. 75, 401\u2013409 (1994).","journal-title":"Circ. Res."},{"key":"4096_CR5","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1093\/cvr\/cvq294","volume":"89","author":"M Shanmugam","year":"2011","unstructured":"Shanmugam, M. et al. Ablation of phospholamban and sarcolipin results in cardiac hypertrophy and decreased cardiac contractility. Cardiovasc. Res. 89, 353\u2013361 (2011).","journal-title":"Cardiovasc. Res."},{"key":"4096_CR6","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1093\/cvr\/cvz205","volume":"116","author":"H Hu","year":"2020","unstructured":"Hu, H. et al. HuR regulates phospholamban expression in isoproterenol-induced cardiac remodelling. Cardiovasc. Res. 116, 944\u2013955 (2020).","journal-title":"Cardiovasc. Res."},{"key":"4096_CR7","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1016\/j.cardiores.2005.04.030","volume":"67","author":"S Kawano","year":"2005","unstructured":"Kawano, S. et al. Blockade of NF-kappaB ameliorates myocardial hypertrophy in response to chronic infusion of angiotensin II. Cardiovasc. Res. 67, 689\u2013698 (2005).","journal-title":"Cardiovasc. Res."},{"key":"4096_CR8","doi-asserted-by":"publisher","first-page":"2108","DOI":"10.1093\/cvr\/cvaa256","volume":"117","author":"C Withaar","year":"2020","unstructured":"Withaar, C. et al. The effects of liraglutide and dapagliflozin on cardiac function and structure in a multi-hit mouse model of heart failure with preserved ejection fraction. Cardiovasc. Res. 117, 2108\u20132124. https:\/\/doi.org\/10.1093\/cvr\/cvaa256 (2020).","journal-title":"Cardiovasc. Res."},{"key":"4096_CR9","doi-asserted-by":"publisher","first-page":"8277","DOI":"10.1073\/pnas.88.18.8277","volume":"88","author":"HA Rockman","year":"1991","unstructured":"Rockman, H. A. et al. Segregation of atrial-specific and inducible expression of an atrial natriuretic factor transgene in an in vivo murine model of cardiac hypertrophy. Proc. Natl. Acad. Sci. USA 88, 8277\u20138281 (1991).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"4096_CR10","first-page":"H2468","volume":"266","author":"HA Rockman","year":"1994","unstructured":"Rockman, H. A., Wachhorst, S. P., Mao, L. & Ross, J. Jr. ANG II receptor blockade prevents ventricular hypertrophy and ANF gene expression with pressure overload in mice. Am. J. Physiol. 266, H2468-2475 (1994).","journal-title":"Am. J. Physiol."},{"key":"4096_CR11","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1093\/cvr\/cvx204","volume":"114","author":"Z Min","year":"2018","unstructured":"Min, Z. et al. Both cardiomyocyte and endothelial cell Nox4 mediate protection against hemodynamic overload-induced remodelling. Cardiovasc. Res. 114, 401\u2013408 (2018).","journal-title":"Cardiovasc. Res."},{"key":"4096_CR12","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/j.jacbts.2019.01.002","volume":"4","author":"H Ueda","year":"2019","unstructured":"Ueda, H. et al. Administration of a TLR9 inhibitor attenuates the development and progression of heart failure in mice. JACC Basic Transl. Sci. 4, 348\u2013363 (2019).","journal-title":"JACC Basic Transl. Sci."},{"key":"4096_CR13","doi-asserted-by":"publisher","first-page":"5844","DOI":"10.1038\/s41598-019-42209-7","volume":"9","author":"DA Richards","year":"2019","unstructured":"Richards, D. A. et al. Distinct phenotypes induced by three degrees of transverse aortic constriction in mice. Sci. Rep. 9, 5844 (2019).","journal-title":"Sci. Rep."},{"key":"4096_CR14","first-page":"1729","volume":"38","author":"AC deAlmeida","year":"2010","unstructured":"deAlmeida, A. C., van Oort, R. J. & Wehrens, X. H. Transverse aortic constriction in mice. J. Vis. Exp. 38, 1729 (2010).","journal-title":"J. Vis. Exp."},{"key":"4096_CR15","doi-asserted-by":"publisher","first-page":"H1261","DOI":"10.1152\/ajpheart.00108.2003","volume":"285","author":"P Hu","year":"2003","unstructured":"Hu, P. et al. Minimally invasive aortic banding in mice: Effects of altered cardiomyocyte insulin signaling during pressure overload. Am. J. Physiol. Heart Circ. Physiol. 285, H1261-1269 (2003).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"4096_CR16","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.carpath.2011.05.002","volume":"21","author":"SF Mohammed","year":"2012","unstructured":"Mohammed, S. F. et al. Variable phenotype in murine transverse aortic constriction. Cardiovasc. Pathol. 21, 188\u2013198 (2012).","journal-title":"Cardiovasc. Pathol."},{"key":"4096_CR17","doi-asserted-by":"publisher","first-page":"H1703","DOI":"10.1152\/ajpheart.00238.2001","volume":"282","author":"Y Liao","year":"2002","unstructured":"Liao, Y. et al. Echocardiographic assessment of LV hypertrophy and function in aortic-banded mice: Necropsy validation. Am. J. Physiol. Heart Circ. Physiol. 282, H1703-1708 (2002).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"4096_CR18","doi-asserted-by":"publisher","first-page":"1680","DOI":"10.1093\/cvr\/cvy141","volume":"114","author":"AO Melleby","year":"2018","unstructured":"Melleby, A. O. et al. A novel method for high precision aortic constriction that allows for generation of specific cardiac phenotypes in mice. Cardiovasc. Res. 114, 1680\u20131690 (2018).","journal-title":"Cardiovasc. Res."},{"key":"4096_CR19","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/978-1-60761-247-6_7","volume":"573","author":"O Tarnavski","year":"2009","unstructured":"Tarnavski, O. Mouse surgical models in cardiovascular research. Methods Mol. Biol. 573, 115\u2013137 (2009).","journal-title":"Methods Mol. Biol."},{"key":"4096_CR20","doi-asserted-by":"publisher","first-page":"H397","DOI":"10.1152\/ajpheart.00088.2013","volume":"305","author":"L Garcia-Menendez","year":"2013","unstructured":"Garcia-Menendez, L., Karamanlidis, G., Kolwicz, S. & Tian, R. Substrain specific response to cardiac pressure overload in C57BL\/6 mice. Am. J. Physiol. Heart Circ. Physiol. 305, H397-402 (2013).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"4096_CR21","doi-asserted-by":"publisher","first-page":"1838","DOI":"10.1093\/cvr\/cvz161","volume":"115","author":"C Riehle","year":"2019","unstructured":"Riehle, C. & Bauersachs, J. Small animal models of heart failure. Cardiovasc. Res. 115, 1838\u20131849 (2019).","journal-title":"Cardiovasc. Res."},{"key":"4096_CR22","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.1016\/j.ajpath.2020.04.006","volume":"190","author":"NA Noll","year":"2020","unstructured":"Noll, N. A., Lal, H. & Merryman, W. D. Mouse models of heart failure with preserved or reduced ejection fraction. Am. J. Pathol. 190, 1596\u20131608 (2020).","journal-title":"Am. J. Pathol."},{"key":"4096_CR23","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1093\/cvr\/cvz016","volume":"116","author":"H Lin","year":"2020","unstructured":"Lin, H. et al. Lansoprazole alleviates pressure overload-induced cardiac hypertrophy and heart failure in mice by blocking the activation of \u03b2-catenin. Cardiovasc. Res. 116, 101\u2013113 (2020).","journal-title":"Cardiovasc. Res."},{"key":"4096_CR24","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1093\/cvr\/cvx221","volume":"114","author":"D Abbadi","year":"2018","unstructured":"Abbadi, D. et al. Local production of tenascin-C acts as a trigger for monocyte\/macrophage recruitment that provokes cardiac dysfunction. Cardiovasc. Res. 114, 123\u2013137 (2018).","journal-title":"Cardiovasc. Res."},{"key":"4096_CR25","doi-asserted-by":"publisher","first-page":"3167","DOI":"10.1038\/s41598-018-21548-x","volume":"8","author":"D Merino","year":"2018","unstructured":"Merino, D. et al. Experimental modelling of cardiac pressure overload hypertrophy: Modified technique for precise, reproducible, safe and easy aortic arch banding-debanding in mice. Sci. Rep. 8, 3167 (2018).","journal-title":"Sci. Rep."},{"key":"4096_CR26","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1111\/j.1748-1716.2011.02369.x","volume":"205","author":"JL Bj\u00f8rnstad","year":"2012","unstructured":"Bj\u00f8rnstad, J. L. et al. A mouse model of reverse cardiac remodelling following banding-debanding of the ascending aorta. Acta Physiol. 205, 92\u2013102 (2012).","journal-title":"Acta Physiol."},{"key":"4096_CR27","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1007\/s00395-005-0546-3","volume":"101","author":"CA Lygate","year":"2006","unstructured":"Lygate, C. A. et al. Serial high resolution 3D-MRI after aortic banding in mice: Band internalization is a source of variability in the hypertrophic response. Basic Res. Cardiol. 101, 8\u201316 (2006).","journal-title":"Basic Res. Cardiol."},{"key":"4096_CR28","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1161\/01.RES.84.6.735","volume":"84","author":"T Meguro","year":"1999","unstructured":"Meguro, T. et al. Cyclosporine attenuates pressure-overload hypertrophy in mice while enhancing susceptibility to decompensation and heart failure. Circ. Res. 84, 735\u2013740 (1999).","journal-title":"Circ. Res."},{"key":"4096_CR29","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1152\/physiolgenomics.00041.2003","volume":"16","author":"O Tarnavski","year":"2004","unstructured":"Tarnavski, O. et al. Mouse cardiac surgery: Comprehensive techniques for the generation of mouse models of human diseases and their application for genomic studies. Physiol. Genom. 16, 349\u2013360 (2004).","journal-title":"Physiol. Genom."},{"key":"4096_CR30","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1161\/HYPERTENSIONAHA.107.088609","volume":"50","author":"R Takahashi","year":"2007","unstructured":"Takahashi, R. et al. Pressure overload-induced cardiomyopathy in heterozygous carrier mice of carnitine transporter gene mutation. Hypertension 50, 497\u2013502 (2007).","journal-title":"Hypertension"},{"key":"4096_CR31","doi-asserted-by":"publisher","first-page":"H987","DOI":"10.1152\/ajpheart.00990.2013","volume":"307","author":"J Liu","year":"2014","unstructured":"Liu, J., Han, P., Xiao, Y., Liu, J. & Kang, Y. J. A novel knot method for individually measurable aortic constriction in rats. Am. J. Physiol. Heart Circ. Physiol. 307, H987-995 (2014).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"4096_CR32","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1161\/CIRCRESAHA.111.243964","volume":"109","author":"C Riehle","year":"2011","unstructured":"Riehle, C. et al. PGC-1\u03b2 deficiency accelerates the transition to heart failure in pressure overload hypertrophy. Circ. Res. 109, 783\u2013793 (2011).","journal-title":"Circ. Res."},{"key":"4096_CR33","doi-asserted-by":"publisher","first-page":"e1000412","DOI":"10.1371\/journal.pbio.1000412","volume":"8","author":"K Carol","year":"2010","unstructured":"Carol, K., William, J., Innes, C., Michael, E. & Douglas, G. Improving bioscience research reporting: The ARRIVE guidelines for reporting animal research. PLoS Biol. 8, e1000412 (2010).","journal-title":"PLoS Biol."}],"updated-by":[{"DOI":"10.1038\/s41598-025-89839-8","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000}}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-04096-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-04096-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-04096-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T08:27:06Z","timestamp":1744705626000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-04096-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,7]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["4096"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-04096-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,7]]},"assertion":[{"value":"4 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 December 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 January 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 April 2025","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41598-025-89839-8","URL":"https:\/\/doi.org\/10.1038\/s41598-025-89839-8","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"85"}}