{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T05:35:36Z","timestamp":1776836136318,"version":"3.51.2"},"reference-count":40,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T00:00:00Z","timestamp":1665705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"DZHK (German Centre for Cardiovascular Research)","award":["DFG"],"award-info":[{"award-number":["DFG"]}]},{"name":"DZHK (German Centre for Cardiovascular Research)","award":["CRC1324"],"award-info":[{"award-number":["CRC1324"]}]},{"name":"DZHK (German Centre for Cardiovascular Research)","award":["Immuno-Fib HF"],"award-info":[{"award-number":["Immuno-Fib HF"]}]},{"name":"German Research Foundation","award":["DFG"],"award-info":[{"award-number":["DFG"]}]},{"name":"German Research Foundation","award":["CRC1324"],"award-info":[{"award-number":["CRC1324"]}]},{"name":"German Research Foundation","award":["Immuno-Fib HF"],"award-info":[{"award-number":["Immuno-Fib HF"]}]},{"DOI":"10.13039\/501100001674","name":"Leducq Foundation","doi-asserted-by":"publisher","award":["DFG"],"award-info":[{"award-number":["DFG"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001674","name":"Leducq Foundation","doi-asserted-by":"publisher","award":["CRC1324"],"award-info":[{"award-number":["CRC1324"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001674","name":"Leducq Foundation","doi-asserted-by":"publisher","award":["Immuno-Fib HF"],"award-info":[{"award-number":["Immuno-Fib HF"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Wnt (a portmanteau of Wingless and Int-1) signaling in the adult heart is largely quiescent. However, there is accumulating evidence that it gets reactivated during the healing process after myocardial infarction (MI). We here tested the therapeutic potential of the Wnt secretion inhibitor LGK-974 on MI healing. Ischemia\/reperfusion (I\/R) injury was induced in mice and Wnt signaling was inhibited by oral administration of the porcupine inhibitor LGK-974. The transcriptome was analyzed from infarcted tissue by using RNA sequencing analysis. The inflammatory response after I\/R was evaluated by flow cytometry. Heart function was assessed by echocardiography and fibrosis by Masson\u2019s trichrome staining. Transcriptome and gene set enrichment analysis revealed a modulation of the inflammatory response upon administration of the Wnt secretion inhibitor LGK-974 following I\/R. In addition, LGK-974-treated animals showed an attenuated inflammatory response and improved heart function. In an in vitro model of hypoxic cardiomyocyte and monocyte\/macrophage interaction, LGK974 inhibited the activation of Wnt signaling in monocytes\/macrophages and reduced their pro-inflammatory phenotype. We here show that Wnt signaling affects inflammatory processes after MI. The Wnt secretion inhibitor LGK-974 appears to be a promising compound for future immunomodulatory approaches to improve cardiac remodeling after MI.<\/jats:p>","DOI":"10.3390\/ijms232012252","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:04:55Z","timestamp":1665965095000},"page":"12252","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Blockade of Wnt Secretion Attenuates Myocardial Ischemia\u2013Reperfusion Injury by Modulating the Inflammatory Response"],"prefix":"10.3390","volume":"23","author":[{"given":"Ingmar S\u00f6ren","family":"Meyer","sequence":"first","affiliation":[{"name":"Internal Medicine III, University Hospital Heidelberg, 69120 Heidelberg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg-Mannheim, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Li","sequence":"additional","affiliation":[{"name":"Internal Medicine III, University Hospital Heidelberg, 69120 Heidelberg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg-Mannheim, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carina","family":"Meyer","sequence":"additional","affiliation":[{"name":"Internal Medicine III, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oksana","family":"Voloshanenko","sequence":"additional","affiliation":[{"name":"German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susann","family":"Pohl","sequence":"additional","affiliation":[{"name":"Internal Medicine III, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Boutros","sequence":"additional","affiliation":[{"name":"German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugo Albert","family":"Katus","sequence":"additional","affiliation":[{"name":"Internal Medicine III, University Hospital Heidelberg, 69120 Heidelberg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg-Mannheim, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norbert","family":"Frey","sequence":"additional","affiliation":[{"name":"Internal Medicine III, University Hospital Heidelberg, 69120 Heidelberg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg-Mannheim, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Leuschner","sequence":"additional","affiliation":[{"name":"Internal Medicine III, University Hospital Heidelberg, 69120 Heidelberg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg-Mannheim, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,14]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2017). 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