{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T06:18:34Z","timestamp":1793513914754,"version":"4.5.0"},"reference-count":34,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T00:00:00Z","timestamp":1718928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Tiroler Wissenschaftsf\u00f6rderung","award":["TWF\u2013F.18815"],"award-info":[{"award-number":["TWF\u2013F.18815"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Activation of the CXCL12\/CXCR4\/ACKR3 axis is known to aid myocardial repair through ischemia-triggered hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1). To enhance the upregulation of HIF-1\u03b1, we administered roxadustat, a novel prolyl hydroxylase inhibitor (PHI) clinically approved by the European Medicines Agency 2021 for the treatment of renal anemia, with the purpose of improving LV function and attenuating ischemic cardiomyopathy. Methods: We evaluated roxadustat\u2019s impact on HIF-1 stimulation, cardiac remodeling, and function after MI. Therefore, we analyzed nuclear HIF-1 expression, the mRNA and protein expression of key HIF-1 target genes (RT-PCR, Western blot), inflammatory cell infiltration (immunohistochemistry), and apoptosis (TUNEL staining) 7 days after MI. Additionally, we performed echocardiography in male and female C57BL\/6 mice 28 days post-MI. Results: We found a substantial increase in nuclear HIF-1, associated with an upregulation of HIF-1\u03b1 target genes like CXCL12\/CXCR4\/ACKR3 at the mRNA and protein levels. Roxadustat increased the proportion of myocardial reparative M2 CD206+ cells, suggesting beneficial alterations in immune cell migration and a trend towards reduced apoptosis. Echocardiography showed that roxadustat treatment significantly preserved ejection fraction and attenuated subsequent ventricular dilatation, thereby reducing adverse remodeling. Conclusions: Our findings suggest that roxadustat is a promising clinically approved treatment option to preserve myocardial function by attenuating adverse remodeling.<\/jats:p>","DOI":"10.3390\/cells13131074","type":"journal-article","created":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T05:33:28Z","timestamp":1718948008000},"page":"1074","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Roxadustat Attenuates Adverse Remodeling Following Myocardial Infarction in Mice"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1074-5463","authenticated-orcid":false,"given":"Marc-Michael","family":"Zaruba","sequence":"first","affiliation":[{"name":"Department of Internal Medicine III, Cardiology and Angiology, Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Staggl","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, Cardiology and Angiology, Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santhosh Kumar","family":"Ghadge","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, Cardiology and Angiology, Medical University Innsbruck, 6020 Innsbruck, Austria"},{"name":"Valneva Austria GmbH, Campus Vienna Biocenter 3, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Maurer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, Cardiology and Angiology, Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmina","family":"Gavranovic-Novakovic","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, Cardiology and Angiology, Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Jeyakumar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, Cardiology and Angiology, Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1786-4058","authenticated-orcid":false,"given":"Patric","family":"Sch\u00f6nherr","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, Cardiology and Angiology, Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Wimmer","sequence":"additional","affiliation":[{"name":"Department of Surgery, Kardinal Schwarzenberg Klinikum GmbH, 5620 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"P\u00f6lzl","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, Cardiology and Angiology, Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, Cardiology and Angiology, Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Messner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, Cardiology and Angiology, Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur. 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