{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T07:03:40Z","timestamp":1789715020034,"version":"4.0.1"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,5,19]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Degenerative mitral regurgitation (MR) is a progressive valvular disorder that causes atrial enlargement, cardiac remodeling, heart failure, and arrhythmias. Current rodent models are limited by thoracotomy or intubation, which increase procedural risk and reduce reproducibility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">We established a minimally invasive, transthoracic echocardiography\u2013guided mouse model of MR by puncturing the anterior mitral leaflet with a 27G needle introduced through the left ventricular apex. Ten\u2010week\u2010old C57BL\/6J mice underwent baseline imaging before MR induction, and sham controls received apical puncture without leaflet disruption. Color Doppler confirmed regurgitant jets and increased vena contracta width, with procedural survival exceeding 90%. At 2\u2009weeks, MR mice exhibited significant left heart enlargement, reduced fractional shortening, and myocardial fibrosis compared with sham. Pressure\u2013volume loop analysis demonstrated increased end\u2010diastolic volume and reduced compliance. RNA sequencing of left atrial tissues revealed enrichment of calcium signaling, apoptosis, and shear stress pathways. Histology confirmed increased cardiomyocyte apoptosis, accompanied by Connexin\u201043 downregulation and elevated ryanodine receptor 2 phosphorylation. Programmed atrial pacing induced atrial fibrillation in MR mice, consistent with enhanced arrhythmogenicity and calcium\u2010handling abnormalities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">This closed\u2010chest, echo\u2010guided murine model reliably induces MR, avoids thoracotomy, and recapitulates key features of human disease, including chamber dilation, fibrosis, and arrhythmia susceptibility. It provides a scalable platform for mechanistic studies, genetic interventions, and drug testing in valvular heart disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.047092","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T09:12:36Z","timestamp":1778058756000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Minimally Invasive, Echocardiography\u2010Guided Mouse Model of Degenerative Mitral Regurgitation Recapitulates Cardiac Remodeling and Arrhythmogenesis"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9525-2144","authenticated-orcid":false,"given":"Wei\u2010Ting","family":"Chang","sequence":"first","affiliation":[{"name":"National Sun Yat\u2010Sen University","place":["Kaohsiung, Taiwan"]},{"name":"Chi\u2010Mei Medical Center","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4142-3635","authenticated-orcid":false,"given":"Nan\u2010Chun","family":"Wu","sequence":"additional","affiliation":[{"name":"Chi Mei Medical Center","place":["Tainan, Taiwan"]},{"name":"Chia Nan University of Pharmacy and Science","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1985-6175","authenticated-orcid":false,"given":"Chin\u2010Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Chi\u2010Mei Medical Center","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8157-1291","authenticated-orcid":false,"given":"Zhih\u2010Cherng","family":"Chen","sequence":"additional","affiliation":[{"name":"National Sun Yat\u2010Sen University","place":["Kaohsiung, Taiwan"]},{"name":"Chi\u2010Mei Medical Center","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Jan","family":"Chen","sequence":"additional","affiliation":[{"name":"Chang\u2010Gung Memorial Hospital Chang\u2010Gung University College of Medicine Tao\u2010yuan","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9288-0580","authenticated-orcid":false,"given":"Jhih\u2010Yuan","family":"Shih","sequence":"additional","affiliation":[{"name":"National Sun Yat\u2010Sen University","place":["Kaohsiung, Taiwan"]},{"name":"Chi\u2010Mei Medical Center","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaf194"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.11.018"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-023-00478-7"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01285"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab368"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.11.022"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000923"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1538\/expanim.18-0045"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCINTERVENTIONS.123.013196"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.4070\/kcj.2011.41.10.603"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.043939"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2015.6554"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.7524"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1159\/000431362"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01380"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.3791\/54110"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.3791\/53810"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.3791\/64168-v"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.019274"},{"key":"e_1_3_2_21_2","first-page":"1652","article-title":"Endoplasmic reticulum stress associated apoptosis implicated in atrial fibrillation","volume":"9","author":"Jianzhou Chen JX","year":"2016","unstructured":"Jianzhou Chen JX, Li G, He G, Tan W, Zhu S, Chen Q, Wu H, Zhang X, Wang L, Xu B. 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