{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T14:01:50Z","timestamp":1793282510656,"version":"4.5.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,9,24]],"date-time":"2012-09-24T00:00:00Z","timestamp":1348444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Familial hypercholesterolaemia (<jats:styled-content style=\"fixed-case\">FH<\/jats:styled-content>) is associated with increased risk of premature atherosclerosis. Inflammation is a key event in atherogenesis, and we have previously reported an inflammatory imbalance between tumour necrosis factor (<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>)\u03b1 and interleukin\u201010 in children with <jats:styled-content style=\"fixed-case\">FH<\/jats:styled-content>. Based on the potential role of <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010related molecules in inflammation, we investigated the regulation of other members of the <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content> superfamily (<jats:styled-content style=\"fixed-case\">TNFSF<\/jats:styled-content>)\/<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content> receptor superfamily (<jats:styled-content style=\"fixed-case\">TNFRSF<\/jats:styled-content>) in children and young adults with <jats:styled-content style=\"fixed-case\">FH<\/jats:styled-content> and matched healthy controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Expression of <jats:italic><jats:styled-content style=\"fixed-case\">TNFSF<\/jats:styled-content><\/jats:italic>\/<jats:italic><jats:styled-content style=\"fixed-case\">TNFRSF<\/jats:styled-content><\/jats:italic> genes in peripheral blood mononuclear cells (<jats:styled-content style=\"fixed-case\">PBMC<\/jats:styled-content>s) was quantified in children and young adults with <jats:styled-content style=\"fixed-case\">FH<\/jats:styled-content> prior to (<jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>42) and after statin treatment (<jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>10) and in controls (<jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>25) by quantitative real\u2010time polymerase chain reaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>First we found that, compared with controls, the <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels of <jats:italic>OX40L, BAFFR<\/jats:italic> and <jats:italic>TRAILR1<\/jats:italic> were significantly higher, whereas <jats:italic>TRAIL<\/jats:italic> and <jats:italic>TRAILR3<\/jats:italic> were significantly lower in children and young adults with <jats:styled-content style=\"fixed-case\">FH<\/jats:styled-content>. Secondly, levels of oxidized low\u2010density lipoprotein (ox<jats:styled-content style=\"fixed-case\">LDL<\/jats:styled-content>) were significantly raised in the <jats:styled-content style=\"fixed-case\">FH<\/jats:styled-content> group, and correlated with the expression of <jats:italic>OX40L<\/jats:italic>,<jats:italic> BAFFR<\/jats:italic> and <jats:italic>TRAILR1<\/jats:italic>. Thirdly, ox<jats:styled-content style=\"fixed-case\">LDL<\/jats:styled-content> increased <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels of <jats:italic>BAFFR, TRAILR1<\/jats:italic> and <jats:italic>TRAILR4<\/jats:italic> in PBMCs <jats:italic>ex vivo<\/jats:italic> from individuals with <jats:styled-content style=\"fixed-case\">FH<\/jats:styled-content>. Fourthly, OX40, acting through OX40L, enhanced the ox<jats:styled-content style=\"fixed-case\">LDL<\/jats:styled-content>\u2010induced expression of matrix metalloproteinase\u20109 in THP\u20101 monocytes <jats:italic>in vitro<\/jats:italic>. Finally, after statin treatment in children with <jats:styled-content style=\"fixed-case\">FH<\/jats:styled-content> (<jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>10), <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels of <jats:italic>OX40L<\/jats:italic> and <jats:italic>TRAILR1<\/jats:italic> decreased, whereas levels <jats:italic>BAFF, TRAIL<\/jats:italic> and <jats:italic>TRAILR3<\/jats:italic> increased.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings suggest the involvement of some <jats:styled-content style=\"fixed-case\">TNFSF<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">TNFRSF<\/jats:styled-content> members and ox<jats:styled-content style=\"fixed-case\">LDL<\/jats:styled-content> in the early stages of atherogenesis; this may potentially contribute to the accelerated rate of atherosclerosis observed in individuals with <jats:styled-content style=\"fixed-case\">FH<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2796.2012.02584.x","type":"journal-article","created":{"date-parts":[[2013,4,12]],"date-time":"2013-04-12T13:53:01Z","timestamp":1365774781000},"page":"69-78","source":"Crossref","is-referenced-by-count":25,"title":["Oxidized <scp>LDL<\/scp> level is related to gene expression of tumour necrosis factor super family members in children and young adults with familial hypercholesterolaemia"],"prefix":"10.1111","volume":"273","author":[{"given":"I.","family":"Narverud","sequence":"first","affiliation":[{"name":"Department of Nutrition Institute for Basic Medical Sciences University of Oslo Oslo Norway"},{"name":"Department of Health, Nutrition and Management Faculty of Health Sciences Oslo and Akershus University College of Applied Sciences Oslo Norway"},{"name":"Lipid Clinic Oslo University Hospital Rikshospitalet Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Halvorsen","sequence":"additional","affiliation":[{"name":"Research Institute for Internal Medicine Oslo University Hospital Rikshospitalet Oslo Norway"},{"name":"Faculty of Medicine University of Oslo Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. S.","family":"Nenseter","sequence":"additional","affiliation":[{"name":"Lipid Clinic Oslo University Hospital Rikshospitalet Oslo Norway"},{"name":"Research Institute for Internal Medicine Oslo University Hospital Rikshospitalet Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Retterst\u00f8l","sequence":"additional","affiliation":[{"name":"Department of Nutrition Institute for Basic Medical Sciences University of Oslo Oslo Norway"},{"name":"Lipid Clinic Oslo University Hospital Rikshospitalet Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Yndestad","sequence":"additional","affiliation":[{"name":"Research Institute for Internal Medicine Oslo University Hospital Rikshospitalet Oslo Norway"},{"name":"Faculty of Medicine University of Oslo Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. 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