Role of phenolic acids in the modulation of monocytes adhesion to endothelial cells and vascular adhesion molecules in a TNF-α stimulated pro-inflammatory environment

Inflammation and oxidative stress are important key factors in the pathogenesis of atherosclerosis [1]. In the last years, specific interest has been shown in the identification of bioactive compounds that can counteract and prevent atherosclerotic processes [2]. Plant derived polyphenol compounds are well known for their antioxidant and anti-inflammatory action with potential important implications in health maintenance and chronic disease risk reduction, including atherosclerosis [3]. The aim of the present study is to evaluate the capacity of several phenolic acids (i.e. gallic, vanillic, chlorogenic, caffeic, ferulic acid and hippuric acid) to counteract the adhesion of monocytes (THP-1) to endothelial cells (HUVEC) in a stimulated pro-inflammatory environment and to reduce the production of cytokines and cell adhesion molecules (VCAM-1, ICAM-1 and E-selectin), as potential markers of such modulation. The adhesion of labelled THP-1 cells to HUVECs is induced by tumor necrosis factor α (TNF-α; 100 ng mL-1). Successively, HUVECs are incubated with different concentrations (from 0.01 to 10 µg mL-1) of phenolic acids for 24 h. The adhesion process and the levels of vascular cell adhesion molecules (VCAM-1, ICAM-1 and E-selectin) are measured. Preliminary experiments show the capacity of gallic acid to counteract the adhesion of monocytes to endothelial cells at 1 μg mL-1 (-23.6%; p<0.001) and 10 μg mL-1 (-27.8%; p<0.001), while vanillic acid only at the maximum concentration (-20.8%; p<0.005). The reduction is associated with a decrease in the levels of E-selectin but not VCAM-1. No significant effect is observed for chlorogenic and caffeic acid. In conclusion, these preliminary experiments support the capacity of phenolic acids to counteract THP-1 adhesion to HUVECs and to reduce the production of E-selectin. However, the results seem to be compound and dose dependent. Further experiments are ongoing in order to better clarify the specific activity of each single compound.. [1] Gimbrone MA Jr, García-Cardeña G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ Res., 2016;118:620-36. [2] Manach C, Milenkovic D, Van de Wiele T, Rodriguez-Mateos A, de Roos B, Garcia-Conesa MT, Landberg R, Gibney ER, Heinonen M, Tomás-Barberán F, Morand C. Addressing the inter-individual variation in response to consumption of plant food bioactives: Towards a better understanding of their role in healthy aging and cardiometabolic risk reduction. Mol Nutr Food Res. 2017 Jun;61(6). doi: 10.1002/mnfr.201600557. [3] Bahramsoltani R, Ebrahimi F, Farzaei MH, Baratpourmoghaddam A, Ahmadi P, Rostamiasrabadi P, Rasouli Amirabadi AH, Rahimi R. Dietary polyphenols for atherosclerosis: A comprehensive review and future perspectives. Crit Rev Food Sci Nutr. 2017;16:1-19.