{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T18:14:16Z","timestamp":1793297656840,"version":"4.5.0"},"reference-count":66,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2023,1,6]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>The osteochondrogenic switch of vascular smooth muscle cells (VSMCs) is a pivotal cellular process in atherosclerotic calcification. However, the exact molecular mechanism of the osteochondrogenic transition of VSMCs remains to be elucidated. Here, we explore the regulatory role of TXNIP (thioredoxin-interacting protein) in the phenotypical transitioning of VSMCs toward osteochondrogenic cells responsible for atherosclerotic calcification.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>\n              The atherosclerotic phenotypes of\n              <jats:italic>Txnip<\/jats:italic>\n              <jats:sup>-\/-<\/jats:sup>\n              mice were analyzed in combination with single-cell RNA-sequencing. The atherosclerotic phenotypes of\n              <jats:italic>Tagln<\/jats:italic>\n              -Cre;\n              <jats:italic>Txnip<\/jats:italic>\n              <jats:sup>flox\/flox<\/jats:sup>\n              mice (smooth muscle cell-specific\n              <jats:italic>Txnip<\/jats:italic>\n              ablation model), and the mice transplanted with the bone marrow of\n              <jats:italic>Txnip<\/jats:italic>\n              <jats:sup>-\/-<\/jats:sup>\n              mice were analyzed. Public single-cell RNA-sequencing dataset (GSE159677) was reanalyzed to define the gene expression of TXNIP in human calcified atherosclerotic plaques. The effect of TXNIP suppression on the osteochondrogenic phenotypic changes in primary aortic VSMCs was analyzed.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Atherosclerotic lesions of\n              <jats:italic>Txnip<\/jats:italic>\n              <jats:sup>-\/-<\/jats:sup>\n              mice presented significantly increased calcification and deposition of collagen content. Subsequent single-cell RNA-sequencing analysis identified the modulated VSMC and osteochondrogenic clusters, which were VSMC-derived populations. The osteochondrogenic cluster was markedly expanded in\n              <jats:italic>Txnip<\/jats:italic>\n              <jats:sup>-\/-<\/jats:sup>\n              mice. The pathway analysis of the VSMC-derived cells revealed enrichment of bone- and cartilage-formation\u2013related pathways and bone morphogenetic protein signaling in\n              <jats:italic>Txnip<\/jats:italic>\n              <jats:sup>-\/-<\/jats:sup>\n              mice. Reanalyzing public single-cell RNA-sequencing dataset revealed that TXNIP was downregulated in the modulated VSMC and osteochondrogenic clusters of human calcified atherosclerotic lesions.\n              <jats:italic>Tagln<\/jats:italic>\n              -Cre;\n              <jats:italic>Txnip<\/jats:italic>\n              <jats:sup>flox\/flox<\/jats:sup>\n              mice recapitulated the calcification and collagen-rich atherosclerotic phenotypes of\n              <jats:italic>Txnip<\/jats:italic>\n              <jats:sup>-\/-<\/jats:sup>\n              mice, whereas the hematopoietic deficiency of TXNIP did not affect the lesion phenotype. Suppression of TXNIP in cultured VSMCs accelerates osteodifferentiation and upregulates bone morphogenetic protein signaling. Treatment with the bone morphogenetic protein signaling inhibitor K02288 abrogated the effect of TXNIP suppression on osteodifferentiation.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Our results suggest that TXNIP is a novel regulator of atherosclerotic calcification by suppressing bone morphogenetic protein signaling to inhibit the transition of VSMCs toward an osteochondrogenic phenotype.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.122.321538","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T10:00:28Z","timestamp":1669802428000},"page":"52-71","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":60,"title":["TXNIP Suppresses the Osteochondrogenic Switch of Vascular Smooth Muscle Cells in Atherosclerosis"],"prefix":"10.1161","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5779-8127","authenticated-orcid":true,"given":"Sang-Ho","family":"Woo","sequence":"first","affiliation":[{"name":"Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Korea (S.-H.W., D.-M.G., J.-S.O., D.-Y.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2910-0120","authenticated-orcid":true,"given":"Dongsoo","family":"Kyung","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Biology and Genomics, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Korea (D.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4876-0477","authenticated-orcid":true,"given":"Seung Hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Life Science, College of Natural Sciences, Research Institute of Natural Sciences, Research Institute for Convergence of Basic Sciences, Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul, Korea (S.H.L., K.S.P., M.K., K.K., J.-H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5016-6995","authenticated-orcid":true,"given":"Kyu Seong","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Life Science, College of Natural Sciences, Research Institute of Natural Sciences, Research Institute for Convergence of Basic Sciences, Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul, Korea (S.H.L., K.S.P., M.K., K.K., J.-H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5482-744X","authenticated-orcid":true,"given":"Minkyu","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Life Science, College of Natural Sciences, Research Institute of Natural Sciences, Research Institute for Convergence of Basic Sciences, Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul, Korea (S.H.L., K.S.P., M.K., K.K., J.-H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4207-9864","authenticated-orcid":true,"given":"Kibyeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Life Science, College of Natural Sciences, Research Institute of Natural Sciences, Research Institute for Convergence of Basic Sciences, Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul, Korea (S.H.L., K.S.P., M.K., K.K., J.-H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo-Jung","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon, Korea 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