{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T20:17:28Z","timestamp":1770754648763,"version":"3.50.0"},"reference-count":32,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T00:00:00Z","timestamp":1611100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18J20623"],"award-info":[{"award-number":["18J20623"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ventricular arrhythmia induced by ischemia\/reperfusion (I\/R) injury is a clinical problem in reperfusion therapies for acute myocardial infarction. Ca2+ overload through reactive oxygen species (ROS) production is a major cause for I\/R-induced arrhythmia. We previously demonstrated that canstatin, a C-terminal fragment of type IV collagen \u03b12 chain, regulated Ca2+ handling in rat heart. In this study, we aimed to clarify the effects of canstatin on I\/R-induced ventricular arrhythmia in rats. Male Wistar rats were subjected to I\/R injury by ligating the left anterior descending artery followed by reperfusion. Ventricular arrhythmia (ventricular tachycardia and ventricular fibrillation) was recorded by electrocardiogram. Nicotinamide adenine dinucleotide phosphate oxidase (NOX) activity and ROS production in neonatal rat cardiomyocytes (NRCMs) stimulated with oxygen glucose deprivation\/reperfusion (OGD\/R) were measured by lucigenin assay and 2\u2032,7\u2032-dichlorodihydrofluorescein diacetate staining, respectively. The H2O2-induced intracellular Ca2+ ([Ca2+]i) rise in NRCMs was measured by a fluorescent Ca2+ indicator. Canstatin (20 \u00b5g\/kg) inhibited I\/R-induced ventricular arrhythmia in rats. Canstatin (250 ng\/mL) inhibited OGD\/R-induced NOX activation and ROS production and suppressed the H2O2-induced [Ca2+]i rise in NRCMs. We for the first time demonstrated that canstatin exerts a preventive effect against I\/R-induced ventricular arrhythmia, perhaps in part through the suppression of ROS production and the subsequent [Ca2+]i rise.<\/jats:p>","DOI":"10.3390\/ijms22031004","type":"journal-article","created":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T12:16:18Z","timestamp":1611144978000},"page":"1004","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Preventive Effect of Canstatin against Ventricular Arrhythmia Induced by Ischemia\/Reperfusion Injury: A Pilot Study"],"prefix":"10.3390","volume":"22","author":[{"given":"Akira","family":"Sugiyama","sequence":"first","affiliation":[{"name":"Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada City, Aomori 034-8628, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yurie","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada City, Aomori 034-8628, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0746-206X","authenticated-orcid":false,"given":"Muneyoshi","family":"Okada","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada City, Aomori 034-8628, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kosuke","family":"Otani","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada City, Aomori 034-8628, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideyuki","family":"Yamawaki","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada City, Aomori 034-8628, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E176","DOI":"10.1161\/ATVBAHA.119.312578","article-title":"Myocardial infarction-From atherosclerosis to thrombosis: Uncovering new diagnostic and therapeutic approaches","volume":"39","author":"Palasubramaniam","year":"2019","journal-title":"Arterioscler. 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