{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T15:40:07Z","timestamp":1776699607740,"version":"3.51.2"},"reference-count":73,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Mild but chronically elevated circulating unconjugated bilirubin is associated with reduced total and low\u2010density lipoprotein cholesterol concentration, which is associated with reduced cardiovascular disease risk. We aimed to investigate whether unconjugated bilirubin influences macrophage cholesterol efflux, as a potential mechanism for the altered circulating lipoprotein concentrations observed in hyperbilirubinemic individuals.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Cholesterol efflux from\n              <jats:styled-content style=\"fixed-case\" toggle=\"no\">THP<\/jats:styled-content>\n              \u20101 macrophages was assessed using plasma obtained from normo\u2010 and hyperbilirubinemic (Gilbert syndrome) humans (n=60 per group) or (heterozygote\/homozygote Gunn) rats (n=20 per group) as an acceptor. Hyperbilirubinemic plasma from patients with Gilbert syndrome and Gunn rats induced significantly reduced cholesterol efflux compared with normobilirubinemic plasma. Unconjugated bilirubin (3\u201317.1\u00a0\u03bcmol\/L) exogenously added to plasma\u2010 or apolipoprotein A1\u2013supplemented media also decreased macrophage cholesterol efflux in a concentration\u2010 and time\u2010dependent manner. We also showed reduced protein expression of the\n              <jats:styled-content style=\"fixed-case\" toggle=\"no\">ATP<\/jats:styled-content>\n              \u2010binding cassette transporter A1 (\n              <jats:styled-content style=\"fixed-case\" toggle=\"no\">ABCA<\/jats:styled-content>\n              1), a transmembrane cholesterol transporter involved in apolipoprotein A1\u2013mediated cholesterol efflux, in\n              <jats:styled-content style=\"fixed-case\" toggle=\"no\">THP<\/jats:styled-content>\n              \u20101 macrophages treated with unconjugated bilirubin and in peripheral blood mononuclear cells obtained from hyperbilirubinemic individuals. Furthermore, we demonstrated that bilirubin accelerates the degradation rate of the\n              <jats:styled-content style=\"fixed-case\" toggle=\"no\">ABCA<\/jats:styled-content>\n              1 protein in\n              <jats:styled-content style=\"fixed-case\" toggle=\"no\">THP<\/jats:styled-content>\n              \u20101 macrophages.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Cholesterol efflux from\n              <jats:styled-content style=\"fixed-case\" toggle=\"no\">THP<\/jats:styled-content>\n              \u20101 macrophages is decreased in the presence of plasma obtained from humans and rats with mild hyperbilirubinemia. A direct effect of unconjugated bilirubin on cholesterol efflux was demonstrated and is associated with decreased\n              <jats:styled-content style=\"fixed-case\" toggle=\"no\">ABCA<\/jats:styled-content>\n              1 protein expression. These data improve our knowledge concerning bilirubin's impact on cholesterol transport and represent an important advancement in our understanding of bilirubin's role in cardiovascular disease.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.117.005520","type":"journal-article","created":{"date-parts":[[2017,4,28]],"date-time":"2017-04-28T20:55:29Z","timestamp":1493412929000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["Bilirubin Decreases Macrophage Cholesterol Efflux and ATP\u2010Binding Cassette Transporter A1 Protein Expression"],"prefix":"10.1161","volume":"6","author":[{"given":"Dongdong","family":"Wang","sequence":"first","affiliation":[{"name":"University of Vienna","place":["Austria"]},{"name":"Institute of Genetics and Animal Breeding of the Polish Academy of Sciences","place":["Jastrzebiec, Poland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anela","family":"Tosevska","sequence":"additional","affiliation":[{"name":"University of Vienna","place":["Austria"]},{"name":"University of Vienna","place":["Austria"]},{"name":"UCLA","place":["Los Angeles"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elke H.","family":"Hei\u00df","sequence":"additional","affiliation":[{"name":"University of Vienna","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Ladurner","sequence":"additional","affiliation":[{"name":"University of Vienna","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"M\u00f6lzer","sequence":"additional","affiliation":[{"name":"University of Vienna","place":["Austria"]},{"name":"University of Aberdeen","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marlies","family":"Wallner","sequence":"additional","affiliation":[{"name":"University of Vienna","place":["Austria"]},{"name":"University of Applied Sciences","place":["Graz, Austria"]},{"name":"FH JOANNEUM","place":["Graz, Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Bulmer","sequence":"additional","affiliation":[{"name":"School of Medical Science and Menzies Health Institute Queensland","place":["Gold Coast, Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl\u2010Heinz","family":"Wagner","sequence":"additional","affiliation":[{"name":"University of Vienna","place":["Austria"]},{"name":"University of Vienna","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Verena M.","family":"Dirsch","sequence":"additional","affiliation":[{"name":"University of Vienna","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atanas G.","family":"Atanasov","sequence":"additional","affiliation":[{"name":"University of Vienna","place":["Austria"]},{"name":"Institute of Genetics and Animal Breeding of the Polish Academy of Sciences","place":["Jastrzebiec, Poland"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1093\/clinchem\/46.11.1723","article-title":"Association of serum bilirubin concentration with risk of coronary artery disease","volume":"46","author":"Mayer M","year":"2000","unstructured":"Mayer M. 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