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We aim to elucidate the effects of TXNIP silencing on vasculogenic properties, paracrine secretion, and neutrophil recruitment under conditions of metabolic stress.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>ECFCs, isolated from human blood cord, were transfected with TXNIP siRNA and exposed to a high glucose and \u03b2-hydroxybutyrate (BHB) medium to simulate metabolic stress. We evaluated the effects of TXNIP silencing on ECFCs\u2019 functional and secretory responses under these conditions. Assessments included analyses of gene and protein expression profiles, vasculogenic properties, cytokine secretion and neutrophil recruitment both in vitro and in vivo. The in vivo effects were examined using a murine model of hindlimb ischemia to observe the physiological relevance of TXNIP modulation under metabolic disorders.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>TXNIP silencing did not mitigate the adverse effects on cell recruitment, vasculogenic properties, or senescence induced by metabolic stress in ECFCs. However, it significantly reduced IL-8 secretion and consequent neutrophil recruitment under these conditions. In a mouse model of hindlimb ischemia, endothelial deletion of TXNIP reduced MIP-2 secretion and prevented increased neutrophil recruitment induced by age-related comorbidities.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our findings suggest that targeting TXNIP in ECFCs may alleviate ischemic complications exacerbated by metabolic stress, offering potential clinical benefits for patients suffering from age-related comorbidities.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13287-024-03850-w","type":"journal-article","created":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T14:29:59Z","timestamp":1722263399000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Targeting TXNIP in endothelial progenitors mitigates IL-8-induced neutrophil recruitment under metabolic stress"],"prefix":"10.1186","volume":"15","author":[{"given":"Julia","family":"Jolibois","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5493-455X","authenticated-orcid":false,"given":"Alison","family":"Domingues","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Divina","family":"El Hamaoui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rapha\u00ebl","family":"Awaida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathilde","family":"Berger-de-Gaillardo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Gu\u00e9rin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M","family":"Smadja","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Perrine","family":"Marquet-DeRoug\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Margaill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Val\u00e9rie","family":"Nivet-Antoine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,7,29]]},"reference":[{"issue":"9331","key":"3850_CR1","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/S0140-6736(02)09670-8","volume":"360","author":"E Tateishi-Yuyama","year":"2002","unstructured":"Tateishi-Yuyama E, Matsubara H, Murohara T, Ikeda U, Shintani S, Masaki H, et al. 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The CRB involves the use of human biological material authorized by the Ministry for a biological resource center for the preparation and provision of human biological material for scientific use. Endothelial colony-forming cells (ECFCs) were isolated from these samples under authorization AC-2016-2759 and last is AC-2022-5325, issued on 19\/12\/22 for a duration of five years. This authorization is not related to a specific project as part of the CRB and therefore does not have a study title or an ethics committee. Blood samples collected on EDTA were obtained from healthy volunteers from Etablissement Fran\u00e7ais du Sang (EFS, convention n\u00b013\/EFS\/064), under the convention entitled \u00ab convention cadre de cession de produits issus du sang ou de ses composants \u00e0 but non th\u00e9rapeutique \u00bb signed by the Etablissement Fran\u00e7ais du Sang and the Universit\u00e9 Paris Cit\u00e9. The donors provided written informed consent. The latest convention is dated 03\/04\/2013 and is renewed implicitly every year. Ethical approval for all animal experiments was obtained from the Ethics Committee on Animal Resources at Paris Descartes University (Paris Descartes University later merged with Paris Diderot University to form Universit\u00e9 Paris Cit\u00e9), and the study was registered with the French Ministry of Higher Education and Research under number #4920 on 12\/05\/2016 (\u201cIsch\u00e9mie du membre inf\u00e9rieur chez des souris invalid\u00e9es (Ec-TXNIP) lors du vieillissement\u201d). This approval and registration were conducted in accordance with Directive 2010\/63\/EU and ARRIVE guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors approved the publication for this manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"225"}}