We have studied the effect of human serum, collected after red wine consumption (RWS), on TNF-α-dependent activation of transcription factors (NF-κB, activator protein-1 (AP-1) and cAMP response element-binding proteins) and on the expression of selected genes involved in cell adhesion or fibrinolysis processes in human primary endothelial cells (human umbilical vein endothelial cells (HUVEC)). Our data indicate that RWS containing RW metabolites, isolated after 40 min from an acute consume of wine (5 ml/kg body weight), induces nuclear translocation of NF-κB and AP-1 in the absence of any further stimulus. On the other hand, TNF-α treatment in the presence of RWS is associated with a delay in transcription factor activation and to a negative modulation on the expression of specific genes. Moreover, RWS stimulates c-jun binding to the tissue-type plasminogen activator cAMP responsive element consensus site modulating the expression of the specific gene downstream. These results confirm that RW metabolites affect the activity of different transcription factors playing an important preconditioning role in the modulation of the inflammatory pathway in endothelial cells. This is the first report on the effects of a complex food matrix, on the molecular mechanisms associated with inflammatory response in HUVEC cultured in condition that reproduces the physiological environment occurring in vivo.

Several food items of plant origin, and in particular red wine, have been reported to protect from cardiovascular disease (CVD) development, thanks to their polyphenol components. Polyphenols undergo complex metabolic transformation during digestion and intestinal absorption. Here we report a novel model to study the effects of complex food matrices, applied to red wine, on gene expression in cultured primary human endothelial cells that takes into account the polyphenol metabolic transformation. Red wine was administered to human volunteers acting as ‘bio-reactors’. Serum (RWS) obtained after 40 min was utilized to enrich endothelial cell culture media. The expression of specific genes involved in cell adhesion (vascular cell adhesion molecule (VCAM), intercellular adhesion molecule (ICAM) and monocytes chemoattractant protein (MCP-1)) and fibrinolysis (tissue-plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and plasminogen activator inhibitor-2 (PAI-2)) was considered as a molecular marker of cell function and related to the effects of RWS. The gene expression profile determined by RWS incubation was significantly different from that observed after the addition of red wine. Data obtained by this approach indicate the importance of taking into account the complex metabolic transformation of polyphenols that occurs during absorption when studying their effect on human health.