Planta Medica International Open 2017; 4(S 01): S1-S202
DOI: 10.1055/s-0037-1608035
Lecture Session – Bioactive Natural Products I
Georg Thieme Verlag KG Stuttgart · New York

Bilirubin Decreases Macrophage Cholesterol Efflux and ABCA1 Protein Expression

D Wang
1   Department of Pharmacognosy, University of Vienna, Vienna, Austria
2   Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, Jastrz? biec, Poland
,
A Tosevska
3   Research Platform Active Ageing, University of Vienna, Vienna, Austria
4   Department of Nutritional Sciences, University of Vienna, Vienna, Austria
5   Department of Molecular, Cell and Developmental Biology, UCLA, Los Angeles, United States
,
E Heiß
1   Department of Pharmacognosy, University of Vienna, Vienna, Austria
,
A Ladurner
1   Department of Pharmacognosy, University of Vienna, Vienna, Austria
,
C Mölzer
4   Department of Nutritional Sciences, University of Vienna, Vienna, Austria
6   School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom
,
M Wallner
4   Department of Nutritional Sciences, University of Vienna, Vienna, Austria
7   Institute of Dietetics and Nutrition, University of Applied Sciences, FH JOANNEUM, Graz, Austria
,
A Bulmer
8   School of Medical Science and Menzies Health Institute Queensland, Gold Coast, Australia
,
KH Wagner
3   Research Platform Active Ageing, University of Vienna, Vienna, Austria
4   Department of Nutritional Sciences, University of Vienna, Vienna, Austria
,
V Dirsch
1   Department of Pharmacognosy, University of Vienna, Vienna, Austria
,
A Atanasov
1   Department of Pharmacognosy, University of Vienna, Vienna, Austria
2   Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, Jastrz? biec, Poland
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Publikationsverlauf

Publikationsdatum:
24. Oktober 2017 (online)

 

Mild, yet chronically elevated circulating unconjugated bilirubin (UCB) is associated with reduced total and LDL-cholesterol concentration, which correlates with reduced cardiovascular disease risk [1, 2]. We aimed to investigate whether UCB influences macrophage cholesterol efflux, as one potential mechanism for the altered circulating lipoprotein concentrations observed in hyperbilirubinemic individuals.

Cholesterol efflux from THP-1 macrophages was assessed using plasma obtained from normo- and hyperbilirubinemic (Gilbert's Syndrome) humans (n = 60/60) or (heterozygote/homozygote Gunn) rats (n = 20/20) as an acceptor. Hyperbilirubinemic plasma from Gilbert's Syndrome individuals and Gunn rats induced a significantly reduced cholesterol efflux compared to normobilirubinemic plasma. UCB (3 – 17.1µmol/L) exogenously added to plasma- or apolipoprotein A1 (apo A1)-supplemented media also decreased macrophage cholesterol efflux in a concentration- and time-dependent manner. We also show a reduced protein expression of the ATP-binding cassette transporter A1 (ABCA1), a transmembrane cholesterol transporter involved in apo A1-mediated cholesterol efflux, in THP-1 macrophages treated with UCB and in peripheral blood mononuclear cells (PBMCs) obtained from hyperbilirubinemic individuals. Furthermore, we demonstrate that bilirubin accelerates the degradation rate of the ABCA1 protein in THP-1 macrophages.

Cholesterol efflux from THP-1 macrophages is decreased in the presence of plasma obtained from humans and rats with mild hyperbilirubinemia. A direct effect of UCB on cholesterol efflux was demonstrated, which is associated with a decreased ABCA1 protein expression. These data improve our knowledge concerning bilirubin's impact on cholesterol transport and represent an important advancement in our understanding of its role in cardiovascular disease.

[1] Mayer M. Clinical Chemistry. 2000; 46: 1723 – 1727.

[2] Bulmer AC, Verkade HJ and Wagner KH. Progress in Lipid Research. 2013; 52: 193 – 205.