Deciphering the Effect of Moderate Wine Consumption on Healthy Aging Through Postprandial Extracellular Vesicles.

Dietary interventions have been consistently proposed as a part of a comprehensive strategy to lower the incidence and severity of atherosclerosis and coronary vascular disease. According to the Dietary Guidelines for Americans 2015-2020, moderate red wine consumption-defined as up to two units of alcohol per day for men and up to one unit of alcohol per day for women-significantly reduces the risk of cardiovascular disease (CVD). Wine is a complex matrix consisting primarily of water (86%) and ethyl alcohol (12%), as well as other different molecules, such as polyphenols, organic acids, tannins, compound minerals, vitamins and biologically active compounds. While most of the nutritional studies have focused on elucidating the mechanisms by which biologically active compounds directly affect cardiovascular-related events, little or nothing is known about the regulatory effect of wine consumption on extracellular vesicles (EVs). EVs are small phospholipid particles that convey molecular bioactive cargoes and play essential roles in intercellular communication and, hence, a multifaceted role in health and disease. Recent advances in research on EVs have significantly enhanced their potential as therapeutic agents for neurological diseases. Owing to their therapeutic properties and ability to cross the blood-brain barrier (BBB), extracellular vesicles are recognized as promising drug delivery vehicles (e.g. polyphenols) for various neurological conditions. For the first time, the purpose of this project is to establish whether the moderate wine consumption may alter the structure, cargo, and functionality of postprandial EVs. In the precision nutrition era, we expect to offer a new insight on EVs and their relationship with wine through the following objectives: 1) To map changes in the lipidome, proteome, polyphenolic cargo, and functional properties of circulating EVs in healthy subjects both at fasting and at postprandial state upon a challenge of a one unit of red or white wine; 2) To analyse the effect of postprandial EVs on atherosclerotic-related events in endothelial and immune cells. 3) To analyse the effect of postprandial EVs on healthy ageing in blood-brain barrier and microglial cells. Collectively, this project will provide fundamental insight into EV biology and remarks the clinical and functional relevance and consequences of moderate wine consumption in health and disease.

• Postprandial changes in extracellular vesicle proteome [Time frame: Baseline (0 hours), postprandial peak (2 hours after beverage intake), and post-peak (6 hours after beverage intake).]
• Postprandial changes in extracellular vesicle lipidome [Time frame: Baseline (0 hours), postprandial peak (2 hours after beverage intake), and post-peak (6 hours after beverage intake).]
• Change from baseline in plasma glucose concentration [Time frame: Baseline (0 hours), 2 hours, and 6 hours after beverage intake]
• Change from baseline in plasma insulin concentration [Time frame: Baseline (0 hours), 2 hours, and 6 hours after beverage intake]
• Change from baseline in plasma triglyceride concentration [Time frame: Baseline (0 hours), 2 hours, and 6 hours after beverage intake]
• Change from baseline in plasma total cholesterol concentration [Time frame: Baseline (0 hours), 2 hours, and 6 hours after beverage intake]
• Change from baseline in plasma HDL cholesterol concentration [Time frame: Baseline (0 hours), 2 hours, and 6 hours after beverage intake]
• Change from baseline in plasma LDL cholesterol concentration [Time frame: Baseline (0 hours), 2 hours, and 6 hours after beverage intake]
• Change from baseline in plasma interleukin-6 (IL-6) concentration [Time frame: Baseline (0 hours), 2 hours, and 6 hours after beverage intake]
• Change from baseline in plasma tumor necrosis factor alpha (TNF-α) concentration [Time frame: Baseline (0 hours), 2 hours, and 6 hours after beverage intake]
• Change from baseline in plasma interleukin-1 beta (IL-1β) concentration [Time frame: Baseline (0 hours), 2 hours, and 6 hours after beverage intake]
• Change from baseline in plasma monocyte chemoattractant protein-1 (MCP-1/CCL2) concentration [Time frame: Baseline (0 hours), 2 hours, and 6 hours after beverage intake]