{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:56:50Z","timestamp":1790877410507,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K12640"],"award-info":[{"award-number":["21K12640"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["26K15617"],"award-info":[{"award-number":["26K15617"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K20886"],"award-info":[{"award-number":["21K20886"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K16125"],"award-info":[{"award-number":["22K16125"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["25K19346"],"award-info":[{"award-number":["25K19346"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"abstract":"\n Abstract<\/jats:title>\n \n Acute myocardial stretch induces reactive oxygen species (ROS) production via NADPH oxidase 2 (NOX2), referred to as stretch\u2010induced ROS. Recently, we demonstrated that stretch\u2010induced ROS serves as a physiological signal in the heart, facilitating calcium release from ryanodine receptors to maintain contractility against acute mechanical load. Chronic mechanical overload triggers oxidative stress, leading to cardiac remodelling and heart failure. Although both conditions are mechanically induced, the relationship between physiology and pathophysiological ROS production remains unclear. To address this issue, we investigated changes in stretch\u2010induced ROS production during the development of transverse aortic constriction (TAC)\u2010induced heart failure in wild\u2010type (WT\u2010TAC) and NOX2 knockout (NOX2 KO\u2010TAC) mice. At 2\u00a0weeks post\u2010TAC, no significant differences were observed in basal ROS levels or cardiac function between the two groups, and cardiac remodelling was evident in neither group. However, stretch\u2010induced ROS production was significantly increased in the WT\u2010TAC group. At 5\u00a0weeks post\u2010TAC, the WT\u2010TAC group progressed to heart failure, reduced ejection fraction with remodelling accompanied by increased basal ROS levels, while no progression was observed in the NOX2 KO\u2010TAC group. The present study demonstrated that in TAC\u2010induced heart failure, physiological acute stretch\u2010induced ROS production increases prior to the elevation of oxidative stress. This suggests that the enhancement of physiological stretch\u2010induced ROS levels in response to chronic pressure overload may induce excessive ROS production, contributing to heart failure. Therefore, pathological oxidative stress may originate from the physiological stretch\u2010induced ROS production pathway.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n Myocardial acute stretch\u2010induced reactive oxygen species (ROS) serves as a physiological signal in the heart, while chronic mechanical overload triggers pathological oxidative stress.<\/jats:p>\n <\/jats:list-item>\n \n Although both conditions are mechanically induced, the relationship between physiology and pathophysiological ROS production remains unclear.<\/jats:p>\n <\/jats:list-item>\n \n We investigated changes in stretch\u2010induced ROS and oxidative stress during the development of pressure overload\u2010induced heart failure using transverse aortic constriction (TAC).<\/jats:p>\n <\/jats:list-item>\n \n TAC\u2010induced chronic pressure overload enhanced physiological acute stretch\u2010induced ROS production prior to the development of oxidative stress and heart failure.<\/jats:p>\n <\/jats:list-item>\n \n The results suggest that pathological oxidative stress in mechanical overload\u2010induced heart failure may originate from physiological acute stretch\u2010induced ROS.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp291314","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:10:16Z","timestamp":1790874616000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Myocardial stretch\u2010induced ROS production is enhanced prior to the development of heart failure under TAC\u2010induced pressure overload"],"prefix":"10.1113","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1078-1646","authenticated-orcid":false,"given":"Yumiko","family":"Chiba","sequence":"first","affiliation":[{"name":"Division of Integrative Cardiovascular Science, Department of Physiology Asahikawa Medical University Asahikawa Hokkaido Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Kaihara","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Diagnostics and Therapeutics, Center for Intractable Disease and ImmunoGenomics (CiDIG) National Institute of Biomedical innovation, Health and Nutrition Ibaraki Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Division of Cardiology and Nephrology, Department of Internal Medicine Asahikawa Medical University Asahikawa Hokkaido Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7601-9654","authenticated-orcid":false,"given":"Gentaro","family":"Iribe","sequence":"additional","affiliation":[{"name":"Division of Integrative Cardiovascular Science, Department of Physiology Asahikawa Medical University Asahikawa Hokkaido Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"e_1_2_5_2_1","first-page":"699","article-title":"Activation of MMP\u20102 as a key event in oxidative stress injury to the heart","volume":"14","author":"Ali M. 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