{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T21:51:25Z","timestamp":1783115485732,"version":"3.54.6"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,10,23]],"date-time":"2021-10-23T00:00:00Z","timestamp":1634947200000},"content-version":"vor","delay-in-days":295,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772112"],"award-info":[{"award-number":["81772112"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>In spite of early interventions to treat acute myocardial infarction (MI), the occurrence of adverse cardiac remodeling following heart failure due to acute MI remains a clinical challenge. Thus, there is an increasing demand for the development of novel therapeutic agents capable of inhibiting the development of pathological ventricular remodeling. RNA\u2010seq data analysis of acute MI rat models from GEO revealed that Runx1 was the most differentially expressed MI\u2010related gene. In this study, we demonstrated that increased Runx1 expression under pathological conditions results in decreased cardiac contractile function. We identified dihydrolycorine, an alkaloid lycorine, as a promising inhibitor of Runx1. Our results showed that treatment with this drug could prevent adverse cardiac remodeling, as indicated by the downregulation of fibrotic genes using western blotting (collagen I, TGF<jats:italic>\u03b2<\/jats:italic>, and p\u2010smad3), downregulation of the apoptosis gene Bax, upregulation of the apoptosis gene Bcl\u20102, and improved cardiac functions, such as LVEF, LVSF, LVESD, and LVEDD. Additionally, dihydrolycorine treatment could rescue cardiomyocyte hypertrophy as demonstrated by wheat germ agglutinin staining, increased expression levels of the punctuate gap junction protein connexin 43, and decreased <jats:italic>\u03b1<\/jats:italic>\u2010SMA expression, resulting in cardiomyocyte fibrosis in immunofluorescence staining. Molecular docking, binding modeling, and pull\u2010down assays were used to identify potential dihydrolycorine\u2010binding sites in Runx1. When Ad\u2010sh\u2010Runx1 was transfected into hypoxia\u2010cardiomyocytes or injected into the hearts of MI rats, the cardioprotective effects of dihydrolycorine were abolished, and the normal electrophysiological activity of cardiomyocytes was disrupted. Taken together, the results of the present study indicate that dihydrolycorine may inhibit adverse cardiac remodeling after MI through the reduction of Runx1, suggesting that dihydrolycorine\u2010mediated\u2010Runx1 regulation might represent a novel therapeutic approach for adverse cardiac remodeling after MI.<\/jats:p>","DOI":"10.1155\/2021\/8528239","type":"journal-article","created":{"date-parts":[[2021,10,23]],"date-time":"2021-10-23T20:20:05Z","timestamp":1635020405000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Dihydrolycorine Attenuates Cardiac Fibrosis and Dysfunction by Downregulating Runx1 following Myocardial Infarction"],"prefix":"10.1155","volume":"2021","author":[{"given":"Tingjuan","family":"Ni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingxiao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunlei","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0569-4182","authenticated-orcid":false,"given":"Zhongqiu","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,23]]},"reference":[{"key":"e_1_2_11_1_2","first-page":"e282","article-title":"2016 ACC\/AHA\/HFSA focused update on new pharmacological therapy for heart failure: an update of the 2013 ACCF\/AHA guideline for the management of heart failure","volume":"13","author":"Members W. 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