{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T04:10:55Z","timestamp":1774498255305,"version":"3.50.1"},"reference-count":51,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>AS, one of the most common forms of valvular heart disease, requiring intervention in aging populations in Europe and North America, has traditionally been viewed as a passive, degenerative condition. However, growing evidence supports a paradigm shift toward recognizing AS as an active metabolic and inflammatory disorder. This narrative review synthesizes experimental, translational, and clinical evidence published between 2015 and 2025 examining metabolic mechanisms linking valvular calcification and atrial remodeling in AS and discusses their clinical relevance in the context of transcatheter aortic valve replacement (TAVR). We discussed classical pathways involving mineral metabolism and vitamin signaling, alongside emerging roles of lipid oxidation, mitochondrial dysfunction, epigenetic regulation, and gut microbiome-derived metabolites. Further, metabolomic signatures associated with disease severity and post-TAVR outcomes were reviewed, highlighting the predominantly associative nature and current limitations of these data. Although valve replacement remains the only effective therapy for advanced AS, metabolic and multi-omics insights may improve future risk stratification and mechanistic understanding. Metabolomic profiling could be integrated at multiple points in the clinical pathway for aortic stenosis and TAVR\u2014most promisingly for pre-procedural risk stratification. The present paper focuses on an integrative framework in which valvular calcification and atrial remodeling are viewed within a broader context of metabolic dysregulation. Future research should aim to translate molecular biomarkers into real-world diagnostics and targeted interventions.<\/jats:p>","DOI":"10.3390\/biom16020251","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T12:51:56Z","timestamp":1770209516000},"page":"251","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Metabolic Drivers of Valve Calcification and Atrial Remodeling in Calcific Aortic Stenosis"],"prefix":"10.3390","volume":"16","author":[{"given":"Simina Mariana","family":"Moroz","sequence":"first","affiliation":[{"name":"Center for Advanced Research in Cardiovascular Pathology and Hemostaseology, Victor Babe\u015f University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"},{"name":"Doctoral School Medicine-Pharmacy, Victor Babe\u015f University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9838-744X","authenticated-orcid":false,"given":"Alina Gabriela","family":"Negru","sequence":"additional","affiliation":[{"name":"Cardiology Department, Victor Babe\u015f University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"},{"name":"Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"},{"name":"Research Center of the Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0859-2498","authenticated-orcid":false,"given":"Silvia","family":"Luca","sequence":"additional","affiliation":[{"name":"Cardiology Department, Victor Babe\u015f University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"},{"name":"Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"},{"name":"Research Center of the Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihaela","family":"Valcovici","sequence":"additional","affiliation":[{"name":"Cardiology Department, Victor Babe\u015f University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"},{"name":"Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"},{"name":"Research Center of the Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirela","family":"Baba","sequence":"additional","affiliation":[{"name":"Doctoral School Medicine-Pharmacy, Victor Babe\u015f University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"},{"name":"Center for Translational Research and Systems Medicine, Victor Babe\u015f University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina Maria","family":"Lupu","sequence":"additional","affiliation":[{"name":"Center for Diagnosis and Study of Parasitic Diseases, Victor Babe\u015f University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"},{"name":"Clinical Laboratory, Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0600-1103","authenticated-orcid":false,"given":"Ana","family":"Lascu","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"},{"name":"Center for Translational Research and Systems Medicine, Victor Babe\u015f University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"},{"name":"Department of Functional Sciences-Pathophysiology, Victor Babe\u015f University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel Florin","family":"Lighezan","sequence":"additional","affiliation":[{"name":"Center for Advanced Research in Cardiovascular Pathology and Hemostaseology, Victor Babe\u015f University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"},{"name":"Department of Internal Medicine I-Medical Semiotics I, Victor Babe\u015f University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6353-7698","authenticated-orcid":false,"given":"Ioana","family":"Mozos","sequence":"additional","affiliation":[{"name":"Center for Translational Research and Systems Medicine, Victor Babe\u015f University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"},{"name":"Department of Functional Sciences-Pathophysiology, Victor Babe\u015f University of Medicine and Pharmacy, 300041 Timi\u0219oara, 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