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We hypothesize that hyperglycemia drives VC through alterations in metabolomic and transcriptomic profiles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human coronary artery smooth muscle cells (SMCs) were cultured with 0, 5.5, and 25\u2009mM glucose under calcifying conditions. Untargeted metabolomic and transcriptomic analyses were performed at different time points. Mitochondrial respiration was examined using Seahorse analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Glucose\u2010treated SMCs promoted extracellular matrix (ECM) calcification in a concentration\u2010 and time\u2010dependent manner. The absence of glucose entirely abolished SMC calcification but reduced SMC proliferation in control and calcifying conditions compared to 25\u2009mM glucose. Multi\u2010omics data integration revealed key players from the hypotaurine\/taurine metabolic pathway as the center hub of the reconstructed network. Glucose promoted the hypotaurine secretion, while its intracellular abundance was not altered. Blocking hypotaurine production by propargylglycine increased ECM calcification, while hypotaurine treatment prevented it. Furthermore, omics data suggest energy remodeling in calcifying SMCs under hyperglycemia. Calcifying SMCs exhibited decreased oxygen consumption that was partially restored by hypotaurine. Validation of our in\u00a0vitro models using the murine warfarin model demonstrated reduced hypotaurine\/taurine transporter (TAUT) expression in SMCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our multi\u2010omics analysis revealed a role of the hypotaurine\/taurine metabolic pathway in glucose\u2010induced SMC calcification. Moreover, our data suggest a glucose\u2010dependent energy remodeling in calcifying SMCs and that increasing glucose concentrations fuel ECM calcification. Our work highlights potential novel therapeutic targets that warrant further investigation in hyperglycemia\u2010dependent in\u00a0vitro SMC calcification.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.70075","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T03:49:04Z","timestamp":1751860144000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Hypotaurine Reduces Glucose\u2010Mediated Vascular Calcification"],"prefix":"10.1111","volume":"241","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5792-1730","authenticated-orcid":false,"given":"Marina A.","family":"Heuschkel","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I \u2013 Cardiology Medical Faculty, RWTH Aachen University  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armand","family":"Jaminon","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Cardiovascular Research Institute Maastricht (CARIM), Maastricht University  Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Gr\u00e4ber","sequence":"additional","affiliation":[{"name":"Helmholtz Institute for Biomedical Engineering, Biointerface Lab  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Artati","sequence":"additional","affiliation":[{"name":"Metabolomics and Proteomics Core Helmholtz Center Munich, German Research Center for Environmental Health  Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerzy","family":"Adamski","sequence":"additional","affiliation":[{"name":"Institute of Experimental Genetics, Helmholtz Center Munich, German Research Center for Environmental Health  Neuherberg Germany"},{"name":"Department of Biochemistry Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubjana  Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4528-2967","authenticated-orcid":false,"given":"Joachim","family":"Jankowski","sequence":"additional","affiliation":[{"name":"Institute for Molecular Cardiovascular Research IMCAR, RWTH Aachen University  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Schurgers","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Cardiovascular Research Institute Maastricht (CARIM), Maastricht University  Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaus","family":"Marx","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I \u2013 Cardiology Medical Faculty, RWTH Aachen University  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willi","family":"Jahnen\u2010Dechent","sequence":"additional","affiliation":[{"name":"Helmholtz Institute for Biomedical Engineering, Biointerface Lab  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7973-1329","authenticated-orcid":false,"given":"Claudia","family":"Goettsch","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I \u2013 Cardiology Medical Faculty, RWTH Aachen University  Aachen Germany"},{"name":"Institute of Physiology, Medical Faculty Carl Gustav Carus, Technical University Dresden  Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.02.010"},{"key":"e_1_2_9_3_1","unstructured":"International Diabetes Federation \u201cIDF Diabetes Atlas\u20147th Edition \u201d (2015) http:\/\/www.diabetesatlas.org."},{"key":"e_1_2_9_4_1","unstructured":"National Center for Chronic Disease Prevention and Health Promotion. 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