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Blueberry Metabolites Attenuate Lipotoxicity‐Induced Endothelial Dysfunction
Author(s) -
Bharat Divya,
Cavalcanti Rafaela Ramos Mororo,
Petersen Chrissa,
Begaye Nathan,
Cutler Brett Ronald,
Costa Marcella Melo Assis,
Ramos Renata Kelly Luna Gomes,
Ferreira Marina Ramos,
Li Youyou,
Bharath Leena P.,
Toolson Emma,
Sebahar Paul,
Looper Ryan E.,
Jalili Thunder,
Rajasekaran Namakkal S.,
Jia Zhenquan,
Symons J. David,
Anandh Babu Pon Velayutham
Publication year - 2018
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201700601
Subject(s) - chemistry , lipotoxicity , endothelial dysfunction , nitric oxide , reactive oxygen species , biochemistry , endothelium , pharmacology , vanillic acid , bilberry , food science , endocrinology , medicine , diabetes mellitus , insulin resistance , organic chemistry
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.