{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:18:45Z","timestamp":1787066325377,"version":"build-2736575974"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T00:00:00Z","timestamp":1677715200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Hyperlipidemia and T cell driven inflammation are important drivers of atherosclerosis, the main underlying cause of cardiovascular disease. Here, we detailed the effects of hyperlipidemia on T cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>In vitro, exposure of human and murine CD4+ T cells to very low-density lipoprotein (VLDL), but not to low-density lipoprotein (LDL) resulted in upregulation of Th1 associated pathways. VLDL was taken up via a CD36-dependent pathway and resulted in membrane stiffening and a reduction in lipid rafts. To further detail this response in vivo, T cells of mice lacking the LDL receptor (LDLr), which develop a strong increase in VLDL cholesterol and triglyceride levels upon high cholesterol feeding were investigated. CD4+ T cells of hyperlipidemic Ldlr-\/- mice exhibited an increased expression of the C-X-C-chemokine receptor 3 (CXCR3) and produced more interferon-\u03b3 (IFN-\u03b3). Gene set enrichment analysis identified IFN-\u03b3-mediated signaling as the most upregulated pathway in hyperlipidemic T cells. However, the classical Th1 associated transcription factor profile with strong upregulation of Tbet and Il12rb2 was not observed. Hyperlipidemia did not affect levels of the CD4+ T cell's metabolites involved in glycolysis or other canonical metabolic pathways but enhanced amino acids levels. However, CD4+ T cells of hyperlipidemic mice showed increased cholesterol accumulation and an increased arachidonic acid (AA) to docosahexaenoic acid (DHA) ratio, which was associated with inflammatory T cell activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Hyperlipidemia, and especially its VLDL component induces an atypical Th1 response in CD4+ T cells. Underlying mechanisms include CD36 mediated uptake of VLDL, and an altered AA\/DHA ratio.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ehjopen\/oead013","type":"journal-article","created":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T02:53:21Z","timestamp":1677812001000},"source":"Crossref","is-referenced-by-count":7,"title":["Hyperlipidaemia elicits an atypical, T helper 1\u2013like CD4+ T-cell response: a key role for very low-density lipoprotein"],"prefix":"10.1093","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2327-0527","authenticated-orcid":false,"given":"Bram W","family":"van Os","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Infection and Immunity, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam , Meibergdreef 9, 1105AZ, Amsterdam , Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winnie G","family":"Vos","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Infection and Immunity, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam , Meibergdreef 9, 1105AZ, Amsterdam , Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A","family":"Bosmans","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Infection and Immunity, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam , Meibergdreef 9, 1105AZ, Amsterdam , Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia M","family":"van Tiel","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Infection and Immunity, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam , Meibergdreef 9, 1105AZ, Amsterdam , Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanne C","family":"Lith","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Infection and Immunity, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam , Meibergdreef 9, 1105AZ, Amsterdam , Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myrthe S","family":"den Toom","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Infection and Immunity, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam , Meibergdreef 9, 1105AZ, Amsterdam , Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Beckers","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Infection and Immunity, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam , Meibergdreef 9, 1105AZ, Amsterdam , Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes H M","family":"Levels","sequence":"additional","affiliation":[{"name":"Department of Experimental Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam , Meibergdreef 9, 1105AZ, Amsterdam , Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne A E","family":"van Wouw","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Infection and Immunity, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam , Meibergdreef 9, 1105AZ, Amsterdam , Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noam","family":"Zelcer","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Infection and Immunity, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam , Meibergdreef 9, 1105AZ, Amsterdam , Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther A","family":"Zaal","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Health Sciences, Division of Cell Biology, Metabolism and Cancer, Faculty of Veterinary Medicine, Utrecht University , Yalelaan 2, 3584CM Utrecht , Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia R","family":"Berkers","sequence":"additional","affiliation":[{"name":"Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Utrecht Institute for Pharmaceutical Sciences, Utrecht University and Netherlands Proteomics Centre , Padualaan 8, 3584CH, Utrecht , Netherlands"},{"name":"Department of Biomolecular Health Sciences, Division of Cell Biology, Metabolism and Cancer, Faculty of Veterinary Medicine, Utrecht University , Yalelaan 2, 3584CM Utrecht , Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris H A","family":"van der Lest","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Health Sciences, Division of Cell Biology, Metabolism and Cancer, Faculty of Veterinary Medicine, Utrecht University , Yalelaan 2, 3584CM Utrecht , Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Bernd","family":"Helms","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Health Sciences, Division of Cell Biology, Metabolism and Cancer, Faculty of Veterinary Medicine, Utrecht University , Yalelaan 2, 3584CM Utrecht , Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4610-8714","authenticated-orcid":false,"given":"Christian","family":"Weber","sequence":"additional","affiliation":[{"name":"Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-Universit\u00e4t , Pettenkoferstra\u00dfe 8a and 9, Munich 80336 , Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance , Pettenkoferstra\u00dfe 8a and 9, Munich 80336 , Germany"},{"name":"Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University , Universiteitssingel 50, Maastricht 6229 ER , Netherlands"},{"name":"Munich Cluster for Systems Neurology (SyNergy), Ludwig Maximilian University of Munich , Feodor-Lynen-Str. 17, 81377 Munich , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothee","family":"Atzler","sequence":"additional","affiliation":[{"name":"Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-Universit\u00e4t , Pettenkoferstra\u00dfe 8a and 9, Munich 80336 , Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance , 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