Modulation of Adhesion Process, E-Selectin and VEGF Production by Anthocyanins and Their Metabolites in an In Vitro Model of Atherosclerosis

Abstract

The present study aims to evaluate the ability of peonidin and petunidin-3-glucoside (Peo-3-glc and Pet-3-glc) and their metabolites (vanillic acid; VA and methyl-gallic acid; MetGA), to prevent monocyte (THP-1) adhesion to endothelial cells (HUVECs), and to reduce the production of vascular cell adhesion molecule (VCAM)-1, E-selectin and vascular endothelial growth factor (VEGF) in a stimulated pro-inflammatory environment, a pivotal step of atherogenesis. Tumor necrosis factor-α (TNF-α; 100 ng mL −1 ) was used to stimulate the adhesion of labelled monocytes (THP-1) to endothelial cells (HUVECs). Successively, different concentrations of Peo-3-glc and Pet-3-glc (0.02 µM, 0.2 µM, 2 µM and 20 µM), VA and MetGA (0.05 µM, 0.5 µM, 5 µM and 50 µM) were tested. After 24 h, VCAM-1, E-selectin and VEGF were quantified by ELISA, while the adhesion process was measured spectrophotometrically. Peo-3-glc and Pet-3-glc (from 0.02 µM to 20 µM) significantly (p < 0.0001) decreased THP-1 adhesion to HUVECs at all concentrations (−37%, −24%, −30% and −47% for Peo-3-glc; −37%, −33%, −33% and −45% for Pet-3-glc). VA, but not MetGA, reduced the adhesion process at 50 µM (−21%; p < 0.001). At the same concentrations, a significant (p < 0.0001) reduction of E-selectin, but not VCAM-1, was documented. In addition, anthocyanins and their metabolites significantly decreased (p < 0.001) VEGF production. The present findings suggest that while Peo-3-glc and Pet-3-glc (but not their metabolites) reduced monocyte adhesion to endothelial cells through suppression of E-selectin production, VEGF production was reduced by both anthocyanins and their metabolites, suggesting a role in the regulation of angiogenesis.

The Role of the VEGF Family in Atherosclerosis Development and Its Potential as Treatment Targets

“…Recently it was shown that peonidin and petunidin, two anthocyanins naturally occurring in berries and grapes, regulate angiogenesis and atherogenesis. In particular, in TNF-α stimulated pro-inflammatory environment, peonidin and petunidin prevent monocyte adhesion to HUVECs, reduce VCAM-1, E-selecting and VEGF production [92]. Not surprisingly, many other natural compounds directly affect the expression of E-selectin and VCAM-1, two crucial adhesion molecules involved in the initiation of the atherosclerotic process [93].…”

Onion and Apple Functional Ingredients Intake Improves Antioxidant and Inflammatory Status and Vascular Injury in Obese Zucker Rats

“…Recently, it was shown that peonidin and petunidin, two anthocyanins naturally occurring in berries and grapes, regulate angiogenesis and atherogenesis. In particular, in a TNF-α stimulated proinflammatory environment, peonidin and petunidin prevent monocyte adhesion to HUVECs, and reduce VCAM-1, E-selectin and VEGF production [ 82 ]. One of the possible mechanisms of regulation of VEGF’s expression and signalling could rely on the direct hydrophobic interaction between VEGF and polyphenol molecules, causing a change in the secondary structure of the protein, thus inhibiting further VEGFR2 signalling [ 83 ].…”

Genetic Association between TNFA Polymorphisms (rs1799964 and rs361525) and Susceptibility to Cancer in Systemic Sclerosis

“…TNF-α also induces the gene expression of vascular cell adhesion molecule 1 (VCAM-1) which play a crucial role in rolling-type mononuclear cell adhesion and neo-intima formation in case of injury and smooth muscle cell proliferation [ 30 , 31 , 32 ]. Furthermore, many other endothelial surface cell adhesion molecules, including endothelial-leucocyte adhesion molecule-1 (ELAM-1), E-selectin, P-selectin and intracellular adhesion molecule 1 (ICAM-1), are increased by TNF-α, facilitating adhesion, the ingress of eosinophils and T cells to the inflammatory locus and an increase in microvascular permeability [ 7 , 32 , 33 , 34 , 35 ].…”