{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:19:57Z","timestamp":1790734797850,"version":"4.1.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T00:00:00Z","timestamp":1628121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770386"],"award-info":[{"award-number":["81770386"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070403"],"award-info":[{"award-number":["82070403"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010256","name":"Science and Technology Program of Guangzhou","doi-asserted-by":"publisher","award":["201707020012"],"award-info":[{"award-number":["201707020012"]}],"id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010256","name":"Science and Technology Program of Guangzhou","doi-asserted-by":"publisher","award":["201804010086"],"award-info":[{"award-number":["201804010086"]}],"id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012245","name":"Science and Technology Program of Guangdong Province","doi-asserted-by":"publisher","award":["2021A0505030031"],"award-info":[{"award-number":["2021A0505030031"]}],"id":[{"id":"10.13039\/501100012245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012245","name":"Science and Technology Program of Guangdong Province","doi-asserted-by":"publisher","award":["2017A050501019"],"award-info":[{"award-number":["2017A050501019"]}],"id":[{"id":"10.13039\/501100012245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018605","name":"Guangzhou Regenerative Medicine and Health Guangdong Laboratory","doi-asserted-by":"publisher","award":["2018GZR110105001"],"award-info":[{"award-number":["2018GZR110105001"]}],"id":[{"id":"10.13039\/501100018605","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Youth Science and Technology Innovation Talent Program of Guangdong TeZhi plan","award":["2019TQ05Y136"],"award-info":[{"award-number":["2019TQ05Y136"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Recent studies have shown that the choline-derived metabolite trimethylamine N-oxide (TMAO) is a biomarker that promotes cardiovascular disease through the induction of inflammation and stress. Inflammatory responses and stress are involved in the progression of calcified aortic valve disease (CAVD). Here, we examined whether TMAO induces the osteogenic differentiation of aortic valve interstitial cells (AVICs) through endoplasmic reticulum (ER) and mitochondrial stress pathways in vitro and in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Plasma TMAO levels were higher in patients with CAVD (n\u2009=\u200969) than in humans without CAVD (n\u2009=\u2009263), as examined by liquid chromatography\u2013tandem mass spectrometry. Western blot and staining probes showed that TMAO-induced an osteogenic response in human AVICs. Moreover, TMAO promoted ER stress, mitochondrial stress, and nuclear factor-\u03baB (NF-\u03baB) activation in vitro. Notably, the TMAO-mediated effects were reversed by the use of ER stress, mitochondrial stress, and NF-\u03baB activation inhibitors and small interfering RNA. Mice treated with supplemental choline in a high-fat diet had markedly increased TMAO levels and aortic valve thicknesses, which were reduced by 3,3-dimethyl-1-butanol (an inhibitor of trimethylamine formation) treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Choline-derived TMAO promotes osteogenic differentiation through ER and mitochondrial stress pathways in vitro and aortic valve lesions in vivo.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvab243","type":"journal-article","created":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T15:12:41Z","timestamp":1628003561000},"page":"2018-2030","source":"Crossref","is-referenced-by-count":50,"title":["Trimethylamine N-oxide induces osteogenic responses in human aortic valve interstitial cells\n                    <i>in vitro<\/i>\n                    and aggravates aortic valve lesions in mice"],"prefix":"10.1093","volume":"118","author":[{"given":"Jiaying","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University , 1838 Northern Guangzhou Ave, Guangzhou, Guangdong 510515, China"},{"name":"Key Laboratory for Organ Failure Research, Ministry of Education of the People\u2019s Republic of China, 1838 Northern Guangzhou Ave, Guangzhou, Guangdong 510515, China"},{"name":"Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, 1838 Northern Guangzhou Ave, Guangzhou, Guangdong 510515,China"},{"name":"Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Haizhu District, Guangzhou, Guangdong 510320, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingchun","family":"Zeng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University , 1838 Northern Guangzhou Ave, Guangzhou, Guangdong 510515, China"},{"name":"Key Laboratory for Organ Failure Research, Ministry of Education of the People\u2019s Republic of China, 1838 Northern Guangzhou Ave, Guangzhou, Guangdong 510515, China"},{"name":"Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, 1838 Northern Guangzhou Ave, Guangzhou, Guangdong 510515,China"},{"name":"Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Haizhu District, Guangzhou, Guangdong 510320, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Cardiology, First affiliated hospital of Sun Yat-Sen University, 58 Zhongshan 2nd Road, Guangzhou, Guangdong 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaopeng","family":"Xian","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University , 1838 Northern Guangzhou Ave, Guangzhou, Guangdong 510515, China"},{"name":"Key Laboratory for Organ Failure Research, Ministry of Education of the People\u2019s Republic of China, 1838 Northern Guangzhou Ave, Guangzhou, Guangdong 510515, China"},{"name":"Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, 1838 Northern Guangzhou Ave, Guangzhou, Guangdong 510515,China"},{"name":"Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Haizhu District, Guangzhou, Guangdong 510320, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuheng","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University , 1838 Northern Guangzhou Ave, Guangzhou, Guangdong 510515, China"},{"name":"Key Laboratory for Organ Failure Research, Ministry of Education of the People\u2019s Republic of China, 1838 Northern Guangzhou Ave, Guangzhou, Guangdong 510515, China"},{"name":"Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, 1838 Northern Guangzhou Ave, Guangzhou, Guangdong 510515,China"},{"name":"Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Haizhu District, Guangzhou, Guangdong 510320, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Zhan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University , 1838 Northern Guangzhou Ave, Guangzhou, Guangdong 510515, China"},{"name":"Key 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China"},{"name":"Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, 1838 Northern Guangzhou Ave, Guangzhou, Guangdong 510515,China"},{"name":"Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Haizhu District, Guangzhou, Guangdong 510320, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Ao","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Colorado Denver, 12700 E. 19th Avenue Campus Box C-320, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianzhong","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Colorado Denver, 12700 E. 19th Avenue Campus Box C-320, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Ren","sequence":"additional","affiliation":[{"name":"Key Laboratory for Organ Failure 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