{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:57:38Z","timestamp":1792670258439,"version":"4.5.0"},"posted":{"date-parts":[[2026,5,26]]},"group-title":"In Review","reference-count":0,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,9,27]]},"abstract":"<title>Abstract<\/title>\n                <p>\n                  Persistent activation of cardiac fibroblasts into myofibroblasts drives excessive extracellular matrix deposition, leading to maladaptive myocardial fibrosis, adverse remodeling and heart failure (HF) progression. Adipocyte enhancer binding protein 1 (AEBP1) and Aortic carboxypeptidase-like protein (ACLP, full-length AEBP1 protein coded by\n                  <italic>AEBP1<\/italic>\n                  ) has been implicated in pathological fibrosis across multiple organs, with tissue-specific knockdown attenuating fibrosis in preclinical models. Although elevated\n                  <italic>AEBP1<\/italic>\n                  expression has been associated with human HF, its role in myocardial fibrosis progression in vivo remains undefined. Here, we demonstrated that\n                  <italic>AEBP1<\/italic>\n                  is a critical mediator of myocardial fibrosis and adverse cardiac remodeling. Fibroblast-specific knockout and cardiac-specific knockdown of\n                  <italic>Aebp1<\/italic>\n                  si gnificantly improved cardiac function and prevented pathological remodeling in murine models of myocardial ischemia and pressure-overload induced injury. In ex vivo human myocardial tissue culture studies, ACLP overexpression in non-failing hearts induced pathological remodeling, whereas\n                  <italic>AEBP1<\/italic>\n                  knockdown in failing human hearts induced structural reverse remodeling. Mechanistically, we also showed that ACLP regulates key pro-fibrotic transcription factors and genes, including MRTFB, RUNX2, SM22 and COL1A1, thereby orchestrating fibroblast activation. Collectively, these findings establish\n                  <italic>AEBP1<\/italic>\n                  as a central driver of myocardial fi brosis and highlights its inhibition as a promising therapeutic strategy to mitigate both acute and chronic HF.\n                <\/p>","DOI":"10.21203\/rs.3.rs-3390276\/v2","type":"posted-content","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T18:57:28Z","timestamp":1779821848000},"source":"Crossref","is-referenced-by-count":1,"title":["Adipocyte Enhancer Binding Protein 1 (AEBP1) Inhibition as a Potential Anti-Fibrotic Therapy in Heart Failure."],"prefix":"10.21203","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5009-2770","authenticated-orcid":false,"given":"Thirupura Sundari","family":"Shankar","sequence":"first","affiliation":[{"name":"University of Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8490-6111","authenticated-orcid":false,"given":"Joseph","family":"Visker","sequence":"additional","affiliation":[{"name":"University of Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6851-0168","authenticated-orcid":false,"given":"Junedh","family":"Amrute","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgiy","family":"Polishchuk","sequence":"additional","affiliation":[{"name":"University of Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ty","family":"Lunde","sequence":"additional","affiliation":[{"name":"University of Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Ling","sequence":"additional","affiliation":[{"name":"University of Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9006-2452","authenticated-orcid":false,"given":"Peter","family":"Ferrin","sequence":"additional","affiliation":[{"name":"University of Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana","family":"Hamouche","sequence":"additional","affiliation":[{"name":"The University of Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Feigle","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander University (FAU)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dallen","family":"Calder","sequence":"additional","affiliation":[{"name":"University of Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Sachse","sequence":"additional","affiliation":[{"name":"University of Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9415-1245","authenticated-orcid":false,"given":"Christos","family":"Kyriakopoulos","sequence":"additional","affiliation":[{"name":"University of Utah School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Maneta","sequence":"additional","affiliation":[{"name":"University of Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Tseliou","sequence":"additional","affiliation":[{"name":"University of Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sutip","family":"Navankasattusas","sequence":"additional","affiliation":[{"name":"University of Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Selzman","sequence":"additional","affiliation":[{"name":"University of Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3127-1693","authenticated-orcid":false,"given":"Thomas","family":"Seidel","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander University Erlangen-N\u00fcrnberg (FAU)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1948-9945","authenticated-orcid":false,"given":"Kory","family":"Lavine","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1223-327X","authenticated-orcid":false,"given":"Stavros","family":"Drakos","sequence":"additional","affiliation":[{"name":"U 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