{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:34:58Z","timestamp":1792787698699,"version":"4.5.0"},"reference-count":56,"publisher":"Frontiers Media SA","issue":"10","license":[{"start":{"date-parts":[[2019,5,29]],"date-time":"2019-05-29T00:00:00Z","timestamp":1559088000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Richard and Edith Strauss Foundation"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Exp Biol Med (Maywood)"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:p>The Hippo-signaling pathway is a mechanism implicated in cardiomyocyte cytoprotection and regeneration after a myocardial infarction. Yes-associated protein 1, the main effector protein of this pathway, acts as a co-transcriptional activator to promote cardiomyocyte proliferation and survival. However, the biological mechanisms by which yes-associated protein 1 protects the heart post-MI are currently unknown. Here, we propose that yes-associated protein 1 plays a critical role in cardiomyocyte cytoprotection after simulated ischemia-reperfusion injury. AC16 human cardiomyocytes were infected with lentiviral plasmids containing normal human yes-associated protein 1 and a constitutively active form of YAP, YAP1S127A. Cells were exposed to ischemia-reperfusion injury using a hypoxic chamber. Hippo-signaling characterization after ischemia-reperfusion injury was performed via Western blotting and reverse transcriptase polymerase chain reaction. Cell viability, apoptosis, and cellular hypertrophy were assessed as a measure of cytoprotection. The GSK3\u03b2 inhibitor CHIR99021 was used to investigate cross-talk between Hippo and Wnt-signaling and their role in cytoprotection after ischemia-reperfusion-injury. Ischemia-reperfusion injury resulted in significant decreased expression of the non-phosphorylated Hippo signaling kinases MST1 and LATS1, along with decreased expression of YAP\/TAZ. Overexpression of yes-associated protein 1 improved cellular viability, while reducing hypertrophy and apoptosis via the ATM\/ATR DNA damage response pathway. Activation of \u03b2-catenin in YAP-infected cardiomyocytes synergistically reduced cellular hypertrophy after ischemia-reperfusion-injury. Our findings indicate that yes-associated protein 1 is cytoprotective in AC16 human cardiomyocytes after ischemia-reperfusion injury, which may be mediated by co-activation of the canonical Wnt\/\u03b2-catenin pathway. Thus, activation of yes-associated protein 1 may be a novel therapeutic to repair the infarcted myocardium.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Impact statement<\/jats:title>\n                    <jats:p>Genetically engineering the cells of the heart after myocardial infarction to display a more regenerative phenotype is a promising therapy for heart failure patients. Here, we support a regenerative role for yes-associated protein 1, the main effector protein of the Hippo signaling pathway, in AC16 human cardiomyocytes as a potential therapeutic gene target for cardiac repair after myocardial infarction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1535370219851243","type":"journal-article","created":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T01:31:51Z","timestamp":1559179911000},"page":"802-812","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["The cytoprotective impact of yes-associated protein 1 after ischemia-reperfusion injury in AC16 human cardiomyocytes"],"prefix":"10.3389","volume":"244","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3974-5136","authenticated-orcid":false,"given":"Kashif","family":"Khan","sequence":"first","affiliation":[{"name":"Cardiology and Cardiac Surgery, McGill University Health Centre, Montreal, Quebec H4AJ1, 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