{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T20:00:24Z","timestamp":1781812824727,"version":"3.54.5"},"reference-count":26,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T00:00:00Z","timestamp":1663113600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["960671"],"award-info":[{"award-number":["960671"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Seed Funding grant from the Department of Medicine at Michigan State University"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Age-related cardiac fibrosis contributes to the development of heart failure with preserved ejection fraction which lacks ideal treatment. Transient receptor potential ankyrin 1 (TRPA1) is an oxidative stress sensor and could attenuate age-related pathologies in invertebrates. The present study aimed to test whether TRPA1 plays a role in age-related cardiac remodeling and dysfunction. The cardiac function and pathology of 12-week-old (young) and 52-week-old (older) <jats:italic>Trpa1<\/jats:italic><jats:sup>-\/-<\/jats:sup> mice and wild-type (WT) littermates were evaluated by echocardiography and histologic analyses. The expression levels of 84 fibrosis-related genes in the heart were measured by quantitative polymerase chain reaction array. Young <jats:italic>Trpa1<\/jats:italic><jats:sup>-\/-<\/jats:sup> and WT mice had similar left ventricular wall thickness, volume, and systolic and diastolic function. Older <jats:italic>Trpa1<\/jats:italic><jats:sup>-\/-<\/jats:sup> mice had significantly increased left ventricular internal diameter and volume and impaired systolic (lower left ventricular ejection fraction) and diastolic (higher E\/A ratio and isovolumetric relaxation time) functions compared with older WT mice (<jats:italic>P<\/jats:italic>&lt;0.05 or <jats:italic>P<\/jats:italic>&lt;0.01). Importantly, older <jats:italic>Trpa1<\/jats:italic><jats:sup>-\/-<\/jats:sup> mice had enhanced cardiac fibrosis than older WT mice (<jats:italic>P<\/jats:italic>&lt;0.05) while the two strains had similar degree of cardiac hypertrophy. Among the 84 fibrosis-related genes, <jats:italic>Acta2<\/jats:italic>, <jats:italic>Inhbe<\/jats:italic>, <jats:italic>Ifng<\/jats:italic>, and <jats:italic>Ccl11<\/jats:italic> were significantly upregulated, while <jats:italic>Timp3<\/jats:italic>, <jats:italic>Stat6<\/jats:italic>, and <jats:italic>Ilk<\/jats:italic> were significantly downregulated in the heart of older <jats:italic>Trpa1<\/jats:italic><jats:sup>-\/-<\/jats:sup> mice compared with older WT mice. Taken together, we found that knocking out <jats:italic>Trpa1<\/jats:italic> accelerated age-related myocardial fibrosis, ventricular dilation, and cardiac dysfunction. These findings suggest that TRPA1 may become a therapeutic target for preventing and\/or treating cardiac fibrosis and heart failure with preserved ejection fraction in the elderly.<\/jats:p>","DOI":"10.1371\/journal.pone.0274618","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T17:53:32Z","timestamp":1663178012000},"page":"e0274618","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Knockout of Trpa1 accelerates age-related cardiac fibrosis and dysfunction"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5790-0291","authenticated-orcid":true,"given":"Shuangtao","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna 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