{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T14:52:28Z","timestamp":1787669548731,"version":"build-2736575974"},"reference-count":97,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"REDNVIA Co., Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Calcific aortic valve disease (CAVD) is an active pathological process driven by complex cellular and molecular mechanisms rather than passive aging. The disease is characterized by endothelial dysfunction, lipid infiltration, inflammation, extracellular matrix remodeling, and osteogenic differentiation of valvular interstitial cells, ultimately leading to hydroxyapatite deposition and progressive valve calcification. Key signaling pathways, including Notch, Wnt\/\u03b2-catenin, BMP2, and TGF-\u03b2, play critical roles in osteogenic reprogramming, while inflammatory cytokines such as IL-6, IL-1\u03b2, and TNF-\u03b1 contribute to a pro-calcific microenvironment. To summarize current knowledge on CAVD pathophysiology and emerging therapeutic strategies, relevant preclinical studies were identified through searches of PubMed, and clinical trials were identified through ClinicalTrials.gov. Evidence indicates that extracellular matrix remodeling, fibrosis, and dysregulated phosphate metabolism, particularly involving TNAP and DPP-4, further accelerate disease progression. Despite advances in understanding disease mechanisms, effective pharmacological therapies remain limited, with the current treatment largely restricted to valve replacement. Emerging therapeutic approaches targeting molecular pathways, including enzyme inhibition, RNA-based therapeutics, and advanced drug delivery systems, may offer promising strategies for disease modification. A deeper understanding of CAVD pathophysiology may facilitate the development of targeted therapies to delay or prevent disease progression.<\/jats:p>","DOI":"10.3390\/cells15060542","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T17:12:26Z","timestamp":1773853946000},"page":"542","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Calcific Aortic Valve Disease: Mechanism and Future Therapeutic Strategies"],"prefix":"10.3390","volume":"15","author":[{"given":"Giwon","family":"Hwang","sequence":"first","affiliation":[{"name":"Research and Development, REDNVIA Co., Ltd., Seoul 06675, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soyoung","family":"Jo","sequence":"additional","affiliation":[{"name":"Research and Development, REDNVIA Co., Ltd., Seoul 06675, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeshin","family":"Kwon","sequence":"additional","affiliation":[{"name":"Research and Development, REDNVIA Co., Ltd., Seoul 06675, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjeong","family":"Kwon","sequence":"additional","affiliation":[{"name":"Research and Development, REDNVIA Co., Ltd., Seoul 06675, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilwhea","family":"Ku","sequence":"additional","affiliation":[{"name":"Research and Development, REDNVIA Co., Ltd., Seoul 06675, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-kwan","family":"Song","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Hwa","family":"Jo","sequence":"additional","affiliation":[{"name":"Research and Development, REDNVIA Co., Ltd., Seoul 06675, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"29464","DOI":"10.1038\/s41598-025-14522-x","article-title":"Global, Regional, and National Burden of Nonrheumatic Calcific Aortic Valve Disease Based on GBD Study 2021","volume":"15","author":"Wang","year":"2025","journal-title":"Sci. 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