{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:20:23Z","timestamp":1760149223923,"version":"build-2065373602"},"reference-count":83,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T00:00:00Z","timestamp":1688688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Robert Bosch Stiftung"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>One of the contributors to atherogenesis is enzymatically modified LDL (eLDL). eLDL was detected in all stages of aortic valve sclerosis and was demonstrated to trigger the activation of p38 mitogen-activated protein kinase (p38 MAPK), which has been identified as a pro-inflammatory protein in atherosclerosis. In this study, we investigated the influence of eLDL on IL-6 and IL-33 induction, and also the impact of eLDL on calcification in aortic valve stenosis (AS). eLDL upregulated phosphate-induced calcification in valvular interstitial cells (VICs)\/myofibroblasts isolated from diseased aortic valves, as demonstrated by alizarin red staining. Functional studies demonstrated activation of p38 MAPK as well as an altered gene expression of osteogenic genes known to be involved in vascular calcification. In parallel with the activation of p38 MAPK, eLDL also induced upregulation of the cytokines IL-6 and IL-33. The results suggest a pro-calcifying role of eLDL in AS via induction of IL-6 and IL-33.<\/jats:p>","DOI":"10.3390\/biom13071091","type":"journal-article","created":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T00:35:21Z","timestamp":1688949321000},"page":"1091","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Pro-Calcifying Role of Enzymatically Modified LDL (eLDL) in Aortic Valve Sclerosis via Induction of IL-6 and IL-33"],"prefix":"10.3390","volume":"13","author":[{"given":"Annemarie","family":"Witz","sequence":"first","affiliation":[{"name":"Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise","family":"Effertz","sequence":"additional","affiliation":[{"name":"Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nora","family":"Goebel","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Robert-Bosch-Hospital, 70376 Stuttgart, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Schwab","sequence":"additional","affiliation":[{"name":"Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, Germany"},{"name":"Department of Clinical Pharmacology, University of Tuebingen, 72076 Tuebingen, Germany"},{"name":"Department of Biochemistry and Pharmacy, University of Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich F. W.","family":"Franke","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Robert-Bosch-Hospital, 70376 Stuttgart, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Torzewski","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Hospital Hygiene, Robert-Bosch-Hospital, 70376 Stuttgart, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/S0140-6736(06)69208-8","article-title":"Burden of valvular heart diseases: A population-based study","volume":"368","author":"Nkomo","year":"2006","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"791646","DOI":"10.3389\/fcvm.2021.791646","article-title":"The Complex Interplay of Inflammation, Metabolism, Epigenetics, and Sex in Calcific Disease of the Aortic Valve","volume":"8","author":"Ferrari","year":"2021","journal-title":"Front. 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