{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T07:46:37Z","timestamp":1777621597602,"version":"3.51.4"},"reference-count":59,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,5,6]],"date-time":"2023-05-06T00:00:00Z","timestamp":1683331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Magnesium deficiency is associated with a greater risk of developing cardiovascular diseases since this cation is fundamental in regulating vascular function. This clinical evidence is sustained by in vitro studies showing that culturing endothelial cells in low concentrations of magnesium promotes the acquisition of a pro-oxidant and pro-inflammatory phenotype. Here, we show that the increase in reactive oxygen species in endothelial cells in low-magnesium-containing medium is due to the upregulation of the pro-oxidant protein thioredoxin interacting protein (TXNIP), with a consequent accumulation of lipid droplets and increase in endothelial permeability through the downregulation and relocalization of junctional proteins. Silencing TXNIP restores the endothelial barrier and lipid content. Because (i) mitochondria serve multiple roles in shaping cell function, health and survival and (ii) mitochondria are the main intracellular stores of magnesium, it is of note that no significant alterations were detected in their morphology and dynamics in our experimental model. We conclude that TXNIP upregulation contributes to low-magnesium-induced endothelial dysfunction in vitro.<\/jats:p>","DOI":"10.3390\/ijms24098351","type":"journal-article","created":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T03:34:53Z","timestamp":1683516893000},"page":"8351","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Role of Txnip in Mediating Low-Magnesium-Driven Endothelial Dysfunction"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4568-7825","authenticated-orcid":false,"given":"Laura","family":"Locatelli","sequence":"first","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, Universit\u00e0 di Milano, Via GB Grassi 74, 20157 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7974-6299","authenticated-orcid":false,"given":"Giorgia","family":"Fedele","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, Universit\u00e0 di Milano, Via GB Grassi 74, 20157 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeanette A.","family":"Maier","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, Universit\u00e0 di Milano, Via GB Grassi 74, 20157 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.atherosclerosis.2016.03.007","article-title":"Vascular endothelium\u2014Gatekeeper of vessel health","volume":"248","author":"Cahill","year":"2016","journal-title":"Atherosclerosis"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kostov, K., and Halacheva, L. 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