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In this study, the ferroptotic effect of TiO<jats:sub>2<\/jats:sub>\u2010NPs (30\u2009nm) at environmentally relevant concentrations (0, 3, 12, and 48\u2009\u03bcg\/mL) on human umbilical vein endothelial cells (HUVECs) and the potential molecular mechanism were studied with the corresponding biochemical and molecular biology assays. The results showed that TiO<jats:sub>2<\/jats:sub>\u2010NPs at the tested concentrations could reduce HUVEC viability, but ferrostatin\u20101 might rescue this reduction in cell viability. Also, TiO<jats:sub>2<\/jats:sub>\u2010NPs exposure increased Fe<jats:sup>2+<\/jats:sup>, reactive oxygen species, and malondialdehyde, but decreased glutathione, mitochondrial membrane potential, and activities of anti\u2010oxidative enzymes (catalase, superoxide dismutase, and glutathione peroxidase) in HUVECs through an integrated signaling pathway. Meanwhile, enhanced p38 protein phosphorylation and keap1 protein and decreased Nrf2 protein phosphorylation with reductions in mRNA expressions of downstream anti\u2010oxidative enzyme genes (catalase, superoxide dismutase, glutathione peroxidase, and phospholipid hydroperoxidase) were identified in the TiO<jats:sub>2<\/jats:sub>\u2010NPs\u2010exposed HUVECs. These indicated that TiO<jats:sub>2<\/jats:sub>\u2010NPs exposure induced ferroptosis in HUVECs via the p38\/keap1 inhibiting Nrf2 pathway. EC ferroptosis will be a promising biomarker for assessing the cardiovascular health risks of environmental contaminants.<\/jats:p>","DOI":"10.1002\/tox.24517","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T05:14:02Z","timestamp":1743743642000},"page":"1173-1183","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Environmentally Relevant Concentrations of Commercial Titanium Dioxide Nanoparticles Induce Ferroptosis in <scp>HUVECs<\/scp>"],"prefix":"10.1002","volume":"40","author":[{"given":"Fangfang","family":"Huang","sequence":"first","affiliation":[{"name":"The Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Heath, School of Public Health Guilin Medical University  Guilin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yashi","family":"Feng","sequence":"additional","affiliation":[{"name":"The Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Heath, School of Public Health Guilin Medical University  Guilin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zi\u2010An","family":"Wang","sequence":"additional","affiliation":[{"name":"The School of Medicine &amp; Holistic Integrative Medicine Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunchang","family":"Cao","sequence":"additional","affiliation":[{"name":"The Department of Molecular Biology, School of Intelligent Medicine and Biotechnology Guilin Medical University  Guilin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiong","family":"Yan","sequence":"additional","affiliation":[{"name":"The Department of Respiratory Diseases Guangzhou No. 12 People's Hospital  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wuxiang","family":"Wang","sequence":"additional","affiliation":[{"name":"The School of Public Health University of South China  Hengyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6757-8275","authenticated-orcid":false,"given":"Shaolong","family":"Feng","sequence":"additional","affiliation":[{"name":"The Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Heath, School of Public Health Guilin Medical University  Guilin China"},{"name":"The School of Public Health University of South China  Hengyang China"},{"name":"The State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry Chinese Academy of Sciences  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11051-013-1692-4"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1016\/j.scitotenv.2018.02.316","article-title":"Dip Coating of Air Purifier Ceramic Honeycombs With Photocatalytic TiO2 Nanoparticles: A Case Study for Occupational Exposure","volume":"630","author":"Koivisto A. 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