{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:10:59Z","timestamp":1790655059209,"version":"4.1.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,4,21]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Aortic stenosis is the most common valvular heart disease, and its progression is accelerated in chronic kidney disease (CKD), where multiple circulating abnormalities worsen its pathophysiology. This study examined the impact of CKD\u2010related aldosterone excess, focusing on mineralocorticoid receptor signaling and its crosstalk with the innate immune pathway mediated by Toll\u2010like receptor 4 (TLR4) in aortic valve (AV) interstitial cells\u00a0and AV\u00a0tissue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">For the study, we conducted in\u00a0vivo studies using a CKD rat model challenged with high phosphate, followed by ex\u00a0vivo analysis of AVs. In parallel, primary rat and human valve interstitial cells\u00a0were used in\u00a0vitro to evaluate inflammatory, fibrotic, and osteogenic responses to aldosterone and to identify the key signaling pathways involved. Human AVs from patients with aortic stenosis were also analyzed. Quantitative polymerase chain reaction, western blot, and ELISA were used to characterize these pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">Mineralocorticoid receptor activation emerged as a central driver of aortic stenosis progression in CKD, promoting valve interstitial cell differentiation, inflammation, fibrosis, and calcification through activation of the TLR4\u2013myeloid differentiation primary response 88 innate immunity pathway in response to aldosterone. Moreover, chemerin was identified as a downstream effector of the mineralocorticoid receptor that activates TLR4, further enhancing remodeling and calcification in AVs\u00a0and valve interstitial cells. These results were corroborated in human stenotic AV samples from patients with CKD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Collectively, the study defines a novel mineralocorticoid receptor\u2013TLR4\u2013chemerin axis that mediates aldosterone\u2010driven inflammatory and calcific processes in CKD, in both a rat model and in\u00a0vitro systems.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.047941","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T20:24:06Z","timestamp":1776371046000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Chemerin Activation of Toll\u2010Like Receptor 4 Drives Mineralocorticoid Receptor\u2013Mediated Aortic Valve Remodeling in Chronic Kidney Disease"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4773-7037","authenticated-orcid":false,"given":"Tania","family":"S\u00e1nchez\u2010Bayuela","sequence":"first","affiliation":[{"name":"UMR ICAN 1166, Sorbonne Universit\u00e9, Institute of Cardiometabolism and Nutrition (ICAN)","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5169-1628","authenticated-orcid":false,"given":"Matthieu","family":"Souli\u00e9","sequence":"additional","affiliation":[{"name":"UMR ICAN 1166, Sorbonne Universit\u00e9, Institute of Cardiometabolism and Nutrition (ICAN)","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7656-4046","authenticated-orcid":false,"given":"Mattie","family":"Garaikoetxea","sequence":"additional","affiliation":[{"name":"Navarrabiomed, Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA)","place":["Pamplona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5627-7653","authenticated-orcid":false,"given":"Amaya","family":"Fern\u00e1ndez\u2010Celis","sequence":"additional","affiliation":[{"name":"Navarrabiomed, Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA)","place":["Pamplona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3728-2606","authenticated-orcid":false,"given":"Natalia","family":"L\u00f3pez\u2010Andr\u00e9s","sequence":"additional","affiliation":[{"name":"Navarrabiomed, Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Universidad P\u00fablica de Navarra (UPNA)","place":["Pamplona, Spain"]},{"name":"CIBERCV, Carlos II Institute of Health","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Jaisser","sequence":"additional","affiliation":[{"name":"UMR ICAN 1166, Sorbonne Universit\u00e9, Institute of Cardiometabolism and Nutrition (ICAN)","place":["Paris, France"]},{"name":"Universit\u00e9 de Lorraine, INSERM Centre d\u2019Investigations Cliniques\u2010Plurith\u00e9matique 1433, UMR 1116, CHRU de Nancy, French\u2010Clinical Research Infrastructure Network (F\u2010CRIN) INI\u2010CRCT","place":["Nancy, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaf194"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00137.2007"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.09.052"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00685"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2019.05.028"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gft310"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehac352"},{"key":"e_1_3_2_9_2","first-page":"S45","article-title":"The renin\u2010angiotensin system in progression, remission and regression of chronic nephropathies","volume":"20","author":"Aros C","year":"2002","unstructured":"Aros C, Remuzzi G. 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