{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T17:17:05Z","timestamp":1784567825120,"version":"3.55.0"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,2,2]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Cardiomyocyte\u2010specific transgenic mice overexpressing S100A6, a member of the family of\n              <jats:styled-content style=\"fixed-case\">EF<\/jats:styled-content>\n              \u2010hand calcium\u2010binding proteins, develop less cardiac hypertrophy, interstitial fibrosis, and myocyte apoptosis after permanent coronary ligation, findings that support S100A6 as a potential therapeutic target after acute myocardial infarction. Our purpose was to investigate S100A6 gene therapy for acute myocardial ischemia\u2010reperfusion.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">We first performed in\u00a0vitro studies to examine the effects of S100A6 overexpression and knockdown in rat neonatal cardiomyocytes. S100A6 overexpression improved calcium transients and protected against apoptosis induced by hypoxia\u2010reoxygenation via enhanced calcineurin activity, whereas knockdown of S100A6 had detrimental effects. For in\u00a0vivo studies, human S100A6 plasmid or empty plasmid was delivered to the left ventricular myocardium by ultrasound\u2010targeted microbubble destruction in Fischer\u2010344 rats 2\u00a0days prior to a 30\u2010minute ligation of the left anterior descending coronary artery followed by reperfusion. Control animals received no therapy. Pretreatment with S100A6 gene therapy yielded a survival advantage compared to empty\u2010plasmid and nontreated controls. S100A6\u2010pretreated animals had reduced infarct size and improved left ventricular systolic function, with less myocyte apoptosis, attenuated cardiac hypertrophy, and less cardiac fibrosis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">S100A6 overexpression by ultrasound\u2010targeted microbubble destruction helps ameliorate myocardial ischemia\u2010reperfusion, resulting in lower mortality and improved left ventricular systolic function post\u2013ischemia\u2010reperfusion via attenuation of apoptosis, reduction in cardiac hypertrophy, and reduced infarct size. Our results indicate that S100A6 is a potential therapeutic target for acute myocardial infarction.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.116.004738","type":"journal-article","created":{"date-parts":[[2017,2,8]],"date-time":"2017-02-08T02:00:22Z","timestamp":1486519222000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":45,"title":["Cardiac Overexpression of S100A6 Attenuates Cardiomyocyte Apoptosis and Reduces Infarct Size After Myocardial Ischemia\u2010Reperfusion"],"prefix":"10.1161","volume":"6","author":[{"given":"Azadeh","family":"Mofid","sequence":"first","affiliation":[{"name":"Division of Cardiology, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadav S.","family":"Newman","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J. 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