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Sex differences in AVS arise in part from sexually dimorphic serum composition that differentially regulate valvular interstitial cell (VIC) myofibroblast activation. However, how individual serum factors contribute to sex-specific drug responses targeting VIC myofibroblast activation remains unknown. Here, we integrate serum proteomic profiling with\n                  <jats:italic>in vitro<\/jats:italic>\n                  drug screening using hydrogel biomaterials to identify sex-specific regulators of antifibrotic drug efficacy. We found that Insulin-like Growth Factor Binding Protein 2 (IGFBP2) serum levels are associated with resistance to the antifibrotic drug Evogliptin only in female VICs cultured with female AVS serum. This mechanism is driven by IGFBP2-mediated activation of Rho\/ROCK and focal adhesion kinase signaling pathways that counteract Evogliptin treatment. Our findings reveal a sex-specific, serum-mediated mechanism of Evogliptin resistance and highlight IGFBP2 as a candidate biomarker for stratifying female AVS patients for Evogliptin treatment. More broadly, these findings underscore the importance of incorporating sex-stratified biomarker analyses into AVS therapeutic development to improve patient-specific treatment recommendations.\n                <\/jats:p>","DOI":"10.64898\/2026.01.16.700010","type":"posted-content","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T03:00:17Z","timestamp":1768964417000},"source":"Crossref","is-referenced-by-count":1,"title":["Circulating biomarkers in serum from aortic valve stenosis patients predict sex-specific drug responses in valve myofibroblasts"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8025-3291","authenticated-orcid":false,"given":"Brandon J.","family":"Vogt","sequence":"first","affiliation":[{"name":"Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA, USA"},{"name":"Sanford Consortium for Regenerative Medicine, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4364-454X","authenticated-orcid":false,"given":"Megan","family":"Chavez","sequence":"additional","affiliation":[{"name":"Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA, USA"},{"name":"Sanford Consortium for Regenerative Medicine, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3637-1992","authenticated-orcid":false,"given":"Nicole E.","family":"F\u00e9lix V\u00e9lez","sequence":"additional","affiliation":[{"name":"Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA, USA"},{"name":"Sanford Consortium for Regenerative Medicine, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3386-7674","authenticated-orcid":false,"given":"Rayyan M.","family":"Gorashi","sequence":"additional","affiliation":[{"name":"Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA, USA"},{"name":"Sanford Consortium for Regenerative Medicine, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7887-964X","authenticated-orcid":false,"given":"Ryan R.","family":"Reeves","sequence":"additional","affiliation":[{"name":"Sulpizio Cardiovascular Center, University of California San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4449-9806","authenticated-orcid":false,"given":"Brian A.","family":"Aguado","sequence":"additional","affiliation":[{"name":"Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA, USA"},{"name":"Sanford Consortium for Regenerative Medicine, La Jolla, CA, USA"},{"name":"Program in Materials Science and Engineering, University of California San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026020608445762000_2026.01.16.700010v1.1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmcibr2200439"},{"key":"2026020608445762000_2026.01.16.700010v1.2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.234138"},{"key":"2026020608445762000_2026.01.16.700010v1.3","doi-asserted-by":"publisher","DOI":"10.1186\/s12947-015-0017-4"},{"key":"2026020608445762000_2026.01.16.700010v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.05.015"},{"key":"2026020608445762000_2026.01.16.700010v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2014.08.053"},{"key":"2026020608445762000_2026.01.16.700010v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-14522-x"},{"key":"2026020608445762000_2026.01.16.700010v1.7","unstructured":"Aortic Stenosis Treatment Market. fact.mr. 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