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Mol Nutr Food Res. 2018 Jan;62(2). doi: 10.1002/mnfr.201700601. Epub 2017 Dec 14.

Blueberry Metabolites Attenuate Lipotoxicity-Induced Endothelial Dysfunction.

Author information

1
Department of Nutrition and Integrative Physiology, College of Health, University of Utah, Salt Lake City, USA.
2
Synthetic and Medicinal Chemistry Core, University of Utah, Salt Lake City, USA.
3
Cardiac Aging and Redox Signaling Laboratory, Division of Molecular and Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, USA.
4
Department of Biology, University of North Carolina at Greensboro, Greensboro, USA.
5
Division of Endocrinology, Metabolism, Diabetes, and Molecular Medicine Program, University of Utah, Salt Lake City, USA.

Abstract

SCOPE:

Lipotoxicity-induced endothelial dysfunction is an important vascular complication associated with diabetes. Clinical studies support the vascular benefits of blueberry anthocyanins, but the underlying mechanism is unclear. The hypothesis that metabolites of blueberry anthocyanins attenuate lipotoxicity-induced endothelial dysfunction was tested.

METHODS AND RESULTS:

Human aortic endothelial cells (HAECs) were treated for 6 h with either: (i) the parent anthocyanins (malvidin-3-glucoside and cyanidin-3-glucoside); or (ii) the blueberry metabolites (hydroxyhippuric acid, hippuric acid, benzoic acid-4-sulfate, isovanillic acid-3-sulfate, and vanillic acid-4-sulfate), at concentrations known to circulate in humans following blueberry consumption. For the last 5 h HAECs were treated with palmitate or vehicle. HAECs treated with palmitate displayed elevated reactive oxygen species generation, increased mRNA expression of NOX4, chemokines, adhesion molecules, and IκBα, exaggerated monocyte binding, and suppressed nitric oxide production. Of note, the damaging effects of palmitate were ameliorated in HAECs treated with blueberry metabolites but not parent anthocyanins. Further, important translational relevance of these results was provided by our observation that palmitate-induced endothelial dysfunction was lessened in arterial segments that incubated concurrently with blueberry metabolites.

CONCLUSION:

The presented findings indicate that the vascular benefits of blueberry anthocyanins are mediated by their metabolites. Blueberries might complement existing therapies to lessen vascular complications.

KEYWORDS:

blueberry metabolites; endothelial dysfunction; inflammation; nitric oxide; vascular effects

PMID:
29024402
DOI:
10.1002/mnfr.201700601

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