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Cardiovascular Research Advance Access first published online on August 25, 2009
This version [Corrected Proof] published online on September 15, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp290
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

Expression of bilitranslocase in the vascular endothelium and its function as a flavonoid transporter

Alessandra Maestro1,{dagger}, Michela Terdoslavich1,{ddagger}, Andreja Vanzo2, Adenike Kuku1,3, Federica Tramer1, Vanessa Nicolin4, Fulvio Micali1, Giuliana Decorti1 and Sabina Passamonti1,*

1 Dipartimento di Scienze della Vita, Università di Trieste, via L. Giorgieri 1, 34127 Trieste, Italy
2 Agricultural Institute of Slovenia, Ljubljana, Slovenia
3 Department of Biochemistry, Obafemi Awolowo University, Ile-Ife, Nigeria
4 Dipartimento Universitario Clinico di Biomedicina, Università di Trieste, Trieste, Italy

* Corresponding author. Tel: +39 0405583680, Fax: +39 0405583691, Email: spassamonti{at}units.it

Aims: Ingestion of flavonoid-rich beverages acutely affects endothelial function, causing vasodilation. This effect might be dependent on flavonoid transport into the endothelium. We investigated flavonoid uptake into vascular endothelial cells and whether this was mediated by bilitranslocase (TC 2.A.65.1.1), a bilirubin-specific membrane carrier that also transports various dietary flavonoids.

Methods and results: Human and rat aortic primary endothelial cells as well as Ea.hy 926 cells were found to express bilitranslocase, as assessed by immunocytochemistry and immunoblotting analysis using anti-sequence bilitranslocase antibodies targeting two distinct extracellular epitopes of the carrier. Bilitranslocase function was tested by measuring the rate of bromosulfophthalein (a standard bilitranslocase transport substrate) uptake into endothelial cells and was inhibited not only by bilitranslocase antibodies but also by quercetin (a flavonol). Similarly, uptake of both quercetin and malvidin 3-glucoside (an anthocyanin) were also found to be antibody-inhibited. Quercetin uptake into cells was inhibited by bilirubin, suggesting flavonoid uptake via a membrane pathway shared with bilirubin.

Conclusion: The uptake of some flavonoids into the vascular endothelium occurs via the bilirubin-specific membrane transporter bilitranslocase. This offers new insights into the vascular effects of both flavonoids and bilirubin.

KEYWORDS Vascular endothelium; Flavonoids; Bilirubin; Membrane transport; Bilitranslocase

Time for primary review: 26 days

{dagger} Present address. IRCCS Burlo Garofolo, 34137 Trieste, Italy.

{ddagger} Present address. Rottapharm Biotech Srl, Centro Ricerche Area Science Park, 34012 Trieste, Italy.


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