{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T14:20:22Z","timestamp":1774621222997,"version":"3.50.1"},"reference-count":55,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t              https:\/\/ror.org\/01cwqze88","award":["HL155762"],"award-info":[{"award-number":["HL155762"]}]},{"name":"National Institute of Health\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t              https:\/\/ror.org\/01cwqze88","award":["HL132871"],"award-info":[{"award-number":["HL132871"]}]},{"name":"National Institute of Health\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t              https:\/\/ror.org\/01cwqze88","award":["HL164453"],"award-info":[{"award-number":["HL164453"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>In patients, extraintestinal manifestations of inflammatory bowel disease (IBD) are attenuated ventricular contractile function and arrhythmia. To determine the mechanism of IBD-induced changes in ventricular function, we used a mouse model of dextran sodium sulfate (3.5% weight\/volume; 7 days)-induced colitis. Changes in cardiac function were quantified in isolated ventricular myocytes (VM) by cell shortening, imaging of [Ca2+]i, reactive oxygen species (ROS), and t-tubular density. During colitis, VMs exhibited attenuated cell-shortening and altered Ca2+-handling properties. A prolonged Ca2+ transient (CaT) rise time correlated with an increased coefficient of variation in the subcellular Ca2+ release and an attenuated t-tubular density. T-tubular loss was accompanied by increased ROS production, calpain-2 (CAPN2) expression, junctophilin-2 (JPH-2) cleavage, and autophagy. Inhibition of Angiotensin-converting enzyme during colitis (Perindopril: 3 mg\/kg\/day) prevented the increase in CAPN2, ROS production, autophagy, and t-tubular remodeling. It failed, however, to restore full length JPH-2. We conclude that, during IBD, the angiotensin II (AngII)-induced loss of t-tubular integrity and altered cellular Ca2+ handling can be prevented by suppression of the AngII-dependent increase in CAPN2 and autophagy and thus suppression of AngII signaling might benefit IBD patients with cardiac manifestations of the disease.<\/jats:p>","DOI":"10.3390\/biom16040503","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:45:53Z","timestamp":1774615553000},"page":"503","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Active Colitis Attenuates Ventricular Excitation\u2013Contraction Coupling by T-Tubular Remodeling"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0766-7472","authenticated-orcid":false,"given":"Edward J.","family":"Ouille V","sequence":"first","affiliation":[{"name":"Department of Internal Medicine\/Cardiology, Rush University Medical Center, 1750 W. Harrison St., Chicago, IL 60612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8653-2283","authenticated-orcid":false,"given":"Carlos H.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\/Cardiology, Rush University Medical Center, 1750 W. Harrison St., Chicago, IL 60612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ygor","family":"Marinho","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\/Cardiology, Rush University Medical Center, 1750 W. Harrison St., Chicago, IL 60612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3593-1182","authenticated-orcid":false,"given":"Giedrius","family":"Kanaporis","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biophysics, Rush University Medical Center, 1750 W. Harrison St., Chicago, IL 60612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8847-2712","authenticated-orcid":false,"given":"Kathrin","family":"Banach","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\/Cardiology, Rush University Medical Center, 1750 W. Harrison St., Chicago, IL 60612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.1097\/MIB.0000000000000392","article-title":"Extraintestinal Manifestations of Inflammatory Bowel Disease","volume":"21","author":"Vavricka","year":"2015","journal-title":"Inflamm. 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