{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:53:43Z","timestamp":1791262423451,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T00:00:00Z","timestamp":1659052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Miguel Servet","award":["PI18\/01875"],"award-info":[{"award-number":["PI18\/01875"]}]},{"name":"Miguel Servet","award":["PI21\/00280"],"award-info":[{"award-number":["PI21\/00280"]}]},{"name":"Miguel Servet","award":["ULL-MS-P14"],"award-info":[{"award-number":["ULL-MS-P14"]}]},{"name":"Miguel Servet","award":["FI19\/00302"],"award-info":[{"award-number":["FI19\/00302"]}]},{"name":"Miguel Servet","award":["CD19\/00251"],"award-info":[{"award-number":["CD19\/00251"]}]},{"name":"Miguel Servet Foundation PhD studentship","award":["PI18\/01875"],"award-info":[{"award-number":["PI18\/01875"]}]},{"name":"Miguel Servet Foundation PhD studentship","award":["PI21\/00280"],"award-info":[{"award-number":["PI21\/00280"]}]},{"name":"Miguel Servet Foundation PhD studentship","award":["ULL-MS-P14"],"award-info":[{"award-number":["ULL-MS-P14"]}]},{"name":"Miguel Servet Foundation PhD studentship","award":["FI19\/00302"],"award-info":[{"award-number":["FI19\/00302"]}]},{"name":"Miguel Servet Foundation PhD studentship","award":["CD19\/00251"],"award-info":[{"award-number":["CD19\/00251"]}]},{"name":"Margarita Salas postdoctoral fellowship","award":["PI18\/01875"],"award-info":[{"award-number":["PI18\/01875"]}]},{"name":"Margarita Salas postdoctoral fellowship","award":["PI21\/00280"],"award-info":[{"award-number":["PI21\/00280"]}]},{"name":"Margarita Salas postdoctoral fellowship","award":["ULL-MS-P14"],"award-info":[{"award-number":["ULL-MS-P14"]}]},{"name":"Margarita Salas postdoctoral fellowship","award":["FI19\/00302"],"award-info":[{"award-number":["FI19\/00302"]}]},{"name":"Margarita Salas postdoctoral fellowship","award":["CD19\/00251"],"award-info":[{"award-number":["CD19\/00251"]}]},{"name":"PFIS PhD studentship","award":["PI18\/01875"],"award-info":[{"award-number":["PI18\/01875"]}]},{"name":"PFIS PhD studentship","award":["PI21\/00280"],"award-info":[{"award-number":["PI21\/00280"]}]},{"name":"PFIS PhD studentship","award":["ULL-MS-P14"],"award-info":[{"award-number":["ULL-MS-P14"]}]},{"name":"PFIS PhD studentship","award":["FI19\/00302"],"award-info":[{"award-number":["FI19\/00302"]}]},{"name":"PFIS PhD studentship","award":["CD19\/00251"],"award-info":[{"award-number":["CD19\/00251"]}]},{"name":"Sara Borrell postdoctoral fellowship","award":["PI18\/01875"],"award-info":[{"award-number":["PI18\/01875"]}]},{"name":"Sara Borrell postdoctoral fellowship","award":["PI21\/00280"],"award-info":[{"award-number":["PI21\/00280"]}]},{"name":"Sara Borrell postdoctoral fellowship","award":["ULL-MS-P14"],"award-info":[{"award-number":["ULL-MS-P14"]}]},{"name":"Sara Borrell postdoctoral fellowship","award":["FI19\/00302"],"award-info":[{"award-number":["FI19\/00302"]}]},{"name":"Sara Borrell postdoctoral fellowship","award":["CD19\/00251"],"award-info":[{"award-number":["CD19\/00251"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aortic stenosis (AS) is a fibrocalcific disease of the aortic valves (AVs). Sex-differences in AS pathophysiology have recently been described. High levels of fatty acid-binding protein 4 (FAPB4) in atherosclerotic plaques have been associated with increased local inflammation, endothelial dysfunction, and plaque vulnerability. FABP4 pharmacological blockade has been shown to be effective for the treatment of atherosclerosis by modulating metabolic and inflammatory pathways. We aimed to analyze the sex-specific expression of FABP4 in AS and its potential role as a therapeutic target. A total of 226 patients (61.5% men) with severe AS undergoing surgical AV replacement were recruited. The FABP4 levels were increased in the AVs of AS patients compared to the control subjects, showing greater expression in the fibrocalcific regions. Male AVs exhibited higher levels of FABP4 compared to females, correlating with markers of inflammation (IL-6, Rantes), apoptosis (Bax, caspase-3, Bcl-2), and calcification (IL-8, BMP-2 and BMP-4). VICs derived from AS patients showed the basal expression of FABP4 in vitro. Osteogenic media induced upregulation of intracellular and secreted FABP4 levels in male VICs after 7 days, along with increased levels of inflammatory, pro-apoptotic, and osteogenic markers. Treatment with BMS309403, a specific inhibitor of FABP4, prevented from all of these changes. Thus, we propose FABP4 as a new sex-specific pharmacological therapeutic target in AS.<\/jats:p>","DOI":"10.3390\/ijms23158439","type":"journal-article","created":{"date-parts":[[2022,7,31]],"date-time":"2022-07-31T23:37:29Z","timestamp":1659310649000},"page":"8439","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Targeting Fatty Acid-Binding Protein 4 Improves Pathologic Features of Aortic Stenosis"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7656-4046","authenticated-orcid":false,"given":"Mattie","family":"Garaikoetxea","sequence":"first","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), IdISNA, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0341-0956","authenticated-orcid":false,"given":"Ernesto","family":"Mart\u00edn-N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), IdISNA, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adela","family":"Navarro","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), IdISNA, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Matilla","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), IdISNA, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amaya","family":"Fern\u00e1ndez-Celis","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), IdISNA, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Arrieta","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), IdISNA, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amaia","family":"Garc\u00eda-Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), IdISNA, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Gainza","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), IdISNA, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), IdISNA, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3776-4744","authenticated-orcid":false,"given":"Rafael","family":"S\u00e1daba","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), IdISNA, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Jover","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), IdISNA, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"L\u00f3pez-Andr\u00e9s","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA), IdISNA, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1136\/heartjnl-2016-310894","article-title":"Epidemiology of Valvular Heart Disease in a Swedish Nationwide Hospital-Based Register 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