{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T13:05:34Z","timestamp":1784293534042,"version":"3.55.0"},"reference-count":36,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,5,6]],"date-time":"2019-05-06T00:00:00Z","timestamp":1557100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,5,6]],"date-time":"2019-05-06T00:00:00Z","timestamp":1557100800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Acute myocardial infarction (AMI), a severe consequence of coronary atherosclerotic heart disease, is often associated with high mortality and morbidity. Emerging evidence have shown that the inhibition of the extracellular\u2010signal\u2010regulated kinase (ERK) signaling pathway appears to protect against AMI. Epiregulin (EREG) is an autocrine growth factor that is believed to activate the MEK\/ERK signaling pathway. Therefore, the aim of the present study was to determine the expression patterns of EREG in AMI and to further study its effects on AMI induced experimentally in rats focusing on angiogenesis and left ventricular remodeling. Microarray\u2010based gene expression profiling of AMI was used to identify differentially expressed genes. To understand the biological significance of EREG and whether it is involved in AMI disease through the ERK1\/2 signaling pathway, rats after AMI were treated with small interfering RNA (siRNA) against EREG, an ERK1\/2 pathway inhibitor, PD98059, or both of them. The microarray data sets GSE66360 and GSE46395 showed that EREG was robustly induced in AMI. Both siRNA\u2010mediated depletion of EREG and PD98059 treatment were shown to significantly increase infarct size and left ventricular cardiomyocyte loss and enhance left ventricular remodeling. In addition, we also found that the ERK1\/2 signaling pathway was inhibited following siRNA\u2010mediated EREG inhibition and PD98059 could enhance the effects of EREG inhibition on AMI. In conclusion, these findings highlight that the silencing of EREG inhibits angiogenesis and promotes left ventricular remodeling by disrupting the ERK1\/2 signaling pathway, providing a novel therapeutic target for limiting AMI.<\/jats:p>","DOI":"10.1002\/jcp.28503","type":"journal-article","created":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T00:01:47Z","timestamp":1557187307000},"page":"18653-18665","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Functional suppression of Epiregulin impairs angiogenesis and aggravates left ventricular remodeling by disrupting the extracellular\u2010signal\u2010regulated kinase1\/2 signaling pathway in rats after acute myocardial infarction"],"prefix":"10.1002","volume":"234","author":[{"given":"Ying","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Xiangya Hospital, Central South University Changsha P.R. 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