Cyanidin-3-O-β-glucoside induces oxysterol efflux from endothelial cells: role of liver X receptor alpha

Yun Wang; Yuhua Zhang; Xiaoming Wang; Yan Liu; Min Xia

doi:10.1016/j.atherosclerosis.2012.06.004

Cyanidin-3-O-β-glucoside induces oxysterol efflux from endothelial cells: role of liver X receptor alpha

Atherosclerosis. 2012 Aug;223(2):299-305. doi: 10.1016/j.atherosclerosis.2012.06.004. Epub 2012 Jun 16.

Authors

Yun Wang¹, Yuhua Zhang, Xiaoming Wang, Yan Liu, Min Xia

Affiliation

¹ Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province 510080, PR China.

PMID: 22749359
DOI: 10.1016/j.atherosclerosis.2012.06.004

Abstract

Objectives: Oxidized sterols are toxic to endothelial cells and play a central role in promoting atherogenesis. In this study, we evaluated the impact of anthocyanin, a class of flavonoid compounds, on oxysterol efflux from endothelial cells and the underlying mechanism.

Methods and results: The human aortic ECs (HAECs) were incubated with anthocyanin cyanidin-3-O-β-glucoside (C3G) for different times. C3G treatment upregulates ABCG1 and ABCA1 expression in a dose-dependent manner in HAECs. Moreover, C3G promotes the efflux of cholesterol mainly 7-ketocholesterol (7-KC) from HAECs in an ABCG1-dependent manner. As a result, C3G abrogated the 7-KC-mediated increase of reactive oxygen species (ROS) and apoptosis in HAECs. Furthermore, C3G treatment reverses the inhibition of endothelial nitric oxide synthase (eNOS) activity by 7-KC, leading to the preservation of nitric oxide (NO) bioavailability. The induction of ABCG1 and its mediated 7-KC efflux from HAECs by C3G resulted from liver X receptor α (LXRα) activation, which was confirmed by its blockage of ABCG1 expression after pharmacological or small interfering RNA inhibition of LXRα.

Conclusions: These data uncover a novel mechanism by which C3G ameliorates oxysterol-induced oxidative damage on endothelial cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter 1
ATP Binding Cassette Transporter, Subfamily G, Member 1
ATP-Binding Cassette Transporters / genetics
ATP-Binding Cassette Transporters / metabolism
Anthocyanins / pharmacology*
Apoptosis / drug effects
Biological Transport
Cells, Cultured
Cholesterol / metabolism*
Dose-Response Relationship, Drug
Endothelial Cells / drug effects*
Endothelial Cells / metabolism
Endothelial Cells / pathology
Glucosides / pharmacology*
Humans
Ketocholesterols / metabolism
Liver X Receptors
Nitric Oxide / metabolism
Nitric Oxide Synthase Type III / metabolism
Orphan Nuclear Receptors / drug effects*
Orphan Nuclear Receptors / genetics
Orphan Nuclear Receptors / metabolism
Oxidative Stress / drug effects
RNA Interference
RNA, Messenger / metabolism
Reactive Oxygen Species / metabolism
Time Factors
Transfection
Up-Regulation

Substances

ABCA1 protein, human
ABCG1 protein, human
ATP Binding Cassette Transporter 1
ATP Binding Cassette Transporter, Subfamily G, Member 1
ATP-Binding Cassette Transporters
Anthocyanins
Glucosides
Ketocholesterols
Liver X Receptors
NR1H3 protein, human
Orphan Nuclear Receptors
RNA, Messenger
Reactive Oxygen Species
cyanidin-3-O-beta-glucopyranoside
Nitric Oxide
Cholesterol
NOS3 protein, human
Nitric Oxide Synthase Type III
7-ketocholesterol