{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T10:51:39Z","timestamp":1776941499784,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,7,17]],"date-time":"2019-07-17T00:00:00Z","timestamp":1563321600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST-107-2622-B-039-002-CC3"],"award-info":[{"award-number":["MOST-107-2622-B-039-002-CC3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ageing is associated with impaired repair mechanisms in cardiovascular diseases. Macrophages contribute to cardiac fibrosis after myocardial infarction (MI). The phosphatidyl\u2010inositol\u20103\u2010kinase (PI3K) pathway has been shown to play a role in cardiac remodelling after MI. It remained unclear whether <jats:italic>n<\/jats:italic>\u2010butylidenephthalide, a major component of <jats:italic>Angelica sinensis,<\/jats:italic> can attenuate cardiac fibrosis by regulating the PI3K\/signal transducer and activator of transcription 3 (STAT3)\u2010mediated macrophage phenotypes in ageing rats after MI. Twenty\u2010four hours after ligation of the left anterior descending artery, young (2\u2010month\u2010old) and ageing (18\u2010month\u2010old) male Wistar rats were treated with either vehicle or <jats:italic>n<\/jats:italic>\u2010butylidenephthalide for 4\u00a0weeks. There were similar infarct sizes in both age groups. Compared with young rats, ageing rats exhibited significant increased cardiac fibrosis after MI, which can be attenuated after administering <jats:italic>n<\/jats:italic>\u2010butylidenephthalide. MI was associated with decreased activities of PI3K and STAT3 in ageing rats compared with young rats. In both age groups, <jats:italic>n<\/jats:italic>\u2010butylidenephthalide effectively provided a significant increase of STAT3 phosphorylation, STAT3 activity, STAT3 nuclear translocation, myocardial IL\u201010 levels and the percentage of M2c macrophage and a decrease of myofibroblast infiltration. The effects of <jats:italic>n<\/jats:italic>\u2010butylidenephthalide on increased IL\u201010 levels were reversed by LY294002 or S3I\u2010201. Furthermore, LY294002 abolished the STAT3 phosphorylation, whereas PI3K activity was not affected following the inhibition of STAT3. In conclusions, the host environment is responsible for ageing\u2010related myofibroblast dysregulation in response to MI which can be improved by administering <jats:italic>n<\/jats:italic>\u2010butylidenephthalide via macrophage differentiation towards M2 phenotype by targeting the PI3K\/STAT3 axis.<\/jats:p>","DOI":"10.1111\/jcmm.14526","type":"journal-article","created":{"date-parts":[[2019,7,17]],"date-time":"2019-07-17T08:10:50Z","timestamp":1563351050000},"page":"6378-6392","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Targeting the PI3K\/STAT3 axis modulates age\u2010related differences in macrophage phenotype in rats with myocardial infarction"],"prefix":"10.1111","volume":"23","author":[{"given":"Chih\u2010Chan","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Medical Research Chi\u2010Mei Medical Center Tainan 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