Abstract 376: Berry Anthocyanins and Their Metabolite Ameliorate High Glucose-Induced Adhesion of Monocytes to Human Aortic Endothelial Cells by Modulating the Cross-Talk Between eNOS and NFκB Signaling
Introduction: In diabetes, hyperglycemia-induced vascular inflammation, resulting in the adhesion of monocytes to vascular endothelial cells and their subsequent migration into the subendothelial space, plays a major role in the development of atherosclerosis. ROS induce the inflammatory events involved in diabetic vascular disease by suppressing endothelial nitric oxide synthase (eNOS) through activation of Inhibitor κB kinase (IKKβ), an activator of nuclear factor-κB (NFκB).
Aim: To determine the effects of cyanidin-3-glucoside (a major anthocyanin abundant in berry fruits; cyn-3-glu), protocatechuic acid (a major metabolite of anthocyanins; PCA), and bilberry anthocyanins (a mixture of 15 anthocyanins present in bilberry; BBA) on endothelial inflammation induced by hyperglycemia.
Methods: Human aortic endothelial cells (HAEC) were cultured in normal (5 mM) or high-glucose (25 mM) ± 1 nM - 10 μM cyn-3-glu, PCA or BBA for 72 h. Cell adhesion (assessed via fluorescent probe labeled THP-1, a human monocytic cell line), intracellular ROS (assessed via DCFH-DH), mRNA expression of eNOS, NFκB-p65, and IKKβ (assessed via qPCR), and cell viability (assessed via CellTiter-Blue assay) were quantified in response to the described treatments.
Results: Relative to results obtained from HAEC exposed to 5 mM glucose, ROS generation (42±4%), monocyte adhesion (35±2%), NFκB-p65 expression (80±13%), and IKKβ expression (50±11%) were elevated (p<0.05), whereas eNOS expression was suppressed (50±2%; p<0.05), in cells challenged with high-glucose (n=3-4). Cell viability was maintained regardless of the treatment. The effects of high-glucose on ROS generation, monocyte adhesion, and NFκB-p65, IKKβ and eNOS expression were ameliorated by concurrent treatment with cyn-3-glu or PCA (100 nM). Further, BBA treatment improved the effects of high glucose on ROS and monocyte adhesion.
Conclusion: Berry anthocyanins and their metabolite, at concentrations achievable in human plasma by consumption of berry fruits, attenuate glucotoxic vascular inflammation in HAEC by ameliorating NFκB mediated suppression of eNOS signaling. Anthocyanin consumption might be a novel ancillary treatment to prevent vascular complications associated with diabetes.
Author Disclosures: A. Pon Velayutham: None. E. Kim: None. L. Panneerseelan-Bharath: None. V. Muthuswamy: None. T. Jalili: None. R. Namakkal Soorappan: None. J. Symons: None. Z. Jia: None.
- © 2014 by American Heart Association, Inc.