{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T04:10:18Z","timestamp":1791864618507,"version":"4.3.4"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"18","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,9,18]]},"abstract":"\n Background<\/jats:title>\n Stress\u2010induced cell premature senescence participates in a variety of tissue and organ remodeling by secreting such proteins as proinflammatory cytokines, chemokines, and growth factors. However, the role of cardiomyocyte senescence in heart remodeling after acute myocardial infarction has not been thoroughly elucidated to date. Therefore, we sought to clarify the impact of premature myocardial senescence on postinfarction heart function.<\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Senescence markers, including p16\n \n INK<\/jats:sup>\n <\/jats:styled-content>\n 4a<\/jats:sup>\n , p21\n \n CIP<\/jats:sup>\n <\/jats:styled-content>\n 1\/<\/jats:sup>\n \n WAF<\/jats:sup>\n <\/jats:styled-content>\n 1<\/jats:sup>\n , and\n SA<\/jats:styled-content>\n \u2010\u03b2\u2010gal staining, were analyzed in several heart disease models by immunostaining. Both postinfarction mouse hearts and ischemic human myocardium demonstrated increased senescence markers. Additionally, senescence\u2010related secretory phenotype was activated after acute myocardial infarction, which upregulated senescence\u2010related secretory phenotype factors, including\n CCN<\/jats:styled-content>\n family member 1 (\n CCN<\/jats:styled-content>\n 1), interleukin\u20101\u03b1, tumor necrosis factor \u03b1, and monocyte chemoattractant protein\u20101. In vivo, a tail vein injection of\n AAV<\/jats:styled-content>\n 9\u2010\n Gata4<\/jats:italic>\n \u2010sh\n RNA<\/jats:styled-content>\n significantly attenuated senescence\u2010related secretory phenotype secretion and aggravated postinfarction heart dysfunction. Furthermore, among activated senescence\u2010related secretory phenotype factors,\n CCN<\/jats:styled-content>\n 1 administration reduced myofibroblast viability in\u00a0vitro and rescued the deleterious effect of\n AAV<\/jats:styled-content>\n 9\u2010\n Gata4<\/jats:italic>\n \u2010sh\n RNA<\/jats:styled-content>\n in\u00a0vivo.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Myocardial premature senescence was observed in the ischemic hearts and improved postinfarction heart function, partly through the GATA\u2010binding factor 4\u2010\n CCN<\/jats:styled-content>\n 1 pathway.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.118.009111","type":"journal-article","created":{"date-parts":[[2018,9,16]],"date-time":"2018-09-16T15:02:17Z","timestamp":1537110137000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":60,"title":["Postinfarction Hearts Are Protected by Premature Senescent Cardiomyocytes Via 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