{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:08:44Z","timestamp":1790755724506,"version":"4.1.0"},"reference-count":95,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:00:00Z","timestamp":1654819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Calcific Aortic Valve Disease (CAVD) is a fibrocalcific disease. Lipoproteins and oxidized phospholipids play a substantial role in CAVD; the level of Lp(a) has been shown to accelerate the progression of valve calcification. Indeed, oxidized phospholipids carried by Lp(a) into the aortic valve stimulate endothelial dysfunction and promote inflammation. Inflammation and growth factors actively promote the synthesis of the extracellular matrix (ECM) and trigger an osteogenic program. The accumulation of ECM proteins promotes lipid adhesion to valve tissue, which could initiate the osteogenic program in interstitial valve cells. Statin treatment has been shown to have the ability to diminish the death rate in subjects with atherosclerotic impediments by decreasing the serum LDL cholesterol levels. However, the use of HMG-CoA inhibitors (statins) as cholesterol-lowering therapy did not significantly reduce the progression or the severity of aortic valve calcification. However, new clinical trials targeting Lp(a) or PCSK9 are showing promising results in reducing the severity of aortic stenosis. In this review, we discuss the implication of lipids in aortic valve calcification and the current findings on the effect of lipid-lowering therapy in aortic stenosis.<\/jats:p>","DOI":"10.3390\/jcm11123331","type":"journal-article","created":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T10:25:12Z","timestamp":1654856712000},"page":"3331","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Implication of Lipids in Calcified Aortic Valve Pathogenesis: Why Did Statins Fail?"],"prefix":"10.3390","volume":"11","author":[{"given":"Mohamed J.","family":"Nsaibia","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine, Rutgers University, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2483-7660","authenticated-orcid":false,"given":"Anichavezhi","family":"Devendran","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cardiovascular Research Institute, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eshak","family":"Goubaa","sequence":"additional","affiliation":[{"name":"Thomas Jefferson University East Falls, Philadelphia, PA 19144, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4453-9457","authenticated-orcid":false,"given":"Jamal","family":"Bouitbir","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Division of Molecular and Systems Toxicology, University of Basel, 4056 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7233-7409","authenticated-orcid":false,"given":"Romain","family":"Capoulade","sequence":"additional","affiliation":[{"name":"L\u2019institut Du Thorax, Nantes Universit\u00e9, CNRS, INSERM, F-44000 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6468-1269","authenticated-orcid":false,"given":"Rihab","family":"Bouchareb","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16006","DOI":"10.1038\/nrdp.2016.6","article-title":"Calcific aortic stenosis","volume":"2","author":"Lindman","year":"2016","journal-title":"Nat. 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