@article{da550562558e44b796717c352b846e30,
title = "Hypotaurine Reduces Glucose-Mediated Vascular Calcification",
abstract = "Aim: Vascular calcification (VC), a characteristic feature of peripheral artery disease in patients with diabetes and chronic kidney disease, has been associated with poor prognosis. We hypothesize that hyperglycemia drives VC through alterations in metabolomic and transcriptomic profiles. Methods: Human coronary artery smooth muscle cells (SMCs) were cultured with 0, 5.5, and 25 mM glucose under calcifying conditions. Untargeted metabolomic and transcriptomic analyses were performed at different time points. Mitochondrial respiration was examined using Seahorse analysis. Results: Glucose-treated SMCs promoted extracellular matrix (ECM) calcification in a concentration- and time-dependent manner. The absence of glucose entirely abolished SMC calcification but reduced SMC proliferation in control and calcifying conditions compared to 25 mM glucose. Multi-omics 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 vitro models using the murine warfarin model demonstrated reduced hypotaurine/taurine transporter (TAUT) expression in SMCs. Conclusions: Our multi-omics analysis revealed a role of the hypotaurine/taurine metabolic pathway in glucose-induced SMC calcification. Moreover, our data suggest a glucose-dependent 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-dependent in vitro SMC calcification.",
keywords = "hypotaurine, metabolomics, transcriptomics, vascular calcification",
author = "Heuschkel, \{Marina A.\} and Armand Jaminon and Steffen Gr{\"a}ber and Anna Artati and Jerzy Adamski and Joachim Jankowski and Leon Schurgers and Nikolaus Marx and Willi Jahnen-Dechent and Claudia Goettsch",
note = "Funding Information: This work was supported by the Genomics Facility, a core facility of the Interdisciplinary Center for Clinical Research (IZKF) Aachen within the Faculty of Medicine at RWTH Aachen University. Open Access funding enabled and organized by Projekt DEAL. Funding Information: This work was supported by the Deutsche Forschungsgemeinschaft (German Research Foundation) grant GO1804/5\textbackslash{}u20131 and Transregional Collaborative Research Centre TRR 219; project ID 322900939, project C02 to C.G.), by the Deutsche Herzstiftung (F/40/20 to C.G.) and by the Federal Ministry of Education and Research (BMBF) and the Ministry of Culture and Science of the German State of North Rhine\textbackslash{}u2010Westphalia (MKW) under the Excellence Strategy of the Federal Government and the L\textbackslash{}u00E4nder G:(DE\textbackslash{}u201082)EXS\textbackslash{}u2010SF\textbackslash{}u2010OPSF677 to C.G.). Research was in part funded via the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska\textbackslash{}u2010Curie grant agreement no. 722609. Funding: Funding Information: Funding: This work was supported by the Deutsche Forschungsgemeinschaft (German Research Foundation) grant GO1804/5\textbackslash{}u20131 and Transregional Collaborative Research Centre TRR 219; project ID 322900939, project C02 to C.G.), by the Deutsche Herzstiftung (F/40/20 to C.G.) and by the Federal Ministry of Education and Research (BMBF) and the Ministry of Culture and Science of the German State of North Rhine-Westphalia (MKW) under the Excellence Strategy of the Federal Government and the L\textbackslash{}u00E4nder G:(DE-82)EXS-SF-OPSF677 to C.G.). Research was in part funded via the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no. 722609. This work was supported by the Genomics Facility, a core facility of the Interdisciplinary Center for Clinical Research (IZKF) Aachen within the Faculty of Medicine at RWTH Aachen University. Open Access funding enabled and organized by Projekt DEAL. Publisher Copyright: {\textcopyright} 2025 The Author(s). Acta Physiologica published by John Wiley \& Sons Ltd on behalf of Scandinavian Physiological Society.",
year = "2025",
month = aug,
day = "1",
doi = "10.1111/apha.70075",
language = "English",
volume = "241",
journal = "Acta Physiologica",
issn = "1748-1708",
publisher = "John Wiley \& Sons Inc.",
number = "8",
}