The role of autophagy in the prevention of oxidative stress and cardiovascular disease by olive polyphenols.

Atherosclerotic plaque rupture is the leading cause of acute cardiovascular syndromes and is responsible for 3.9 million deaths in Europe every year. Preventive strategies are greatly needed to reduce the health care burden of cardiovascular disease (CVD). It is well-known that the Mediterranean diet results in a lower CVD risk, with virgin olive oil as an important element. Many of the health-promoting effects are ascribed to the olive polyphenols. Over the years, studies have shown that olive polyphenols reduce oxidative stress and inflammation and enhance vascular function. In recent literature, these effects were related to the upregulation of autophagy. Autophagy is a cellular housekeeping mechanism and autophagy deficiency is detrimental in the development of CVD. Thus, inducing autophagy is likely to be an effective preventive strategy. Olive polyphenols were identified as natural autophagy inducers, but further research is needed to define the contribution of this mechanism to their antioxidant and atheroprotective effects. Therefore, we will determine the most potent autophagy-inducing olive polyphenol in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) and define the underlying molecular mechanisms linked to autophagy. The most potent polyphenol will be selected for further in vivo analysis, in which we will identify its effects on the functionality of healthy blood vessels, CVD prevention and oxidative stress, with a special focus on the role of EC and VSMC autophagy. This project will give insight in the mechanism of action of olive polyphenols and is an important step towards the implementation of olive polyphenol-based nutraceuticals for the prevention of CVD.

Keywords:AUTOPHAGY, OXIDATIVE STRESS, ATHEROSCLEROSIS, POLYPHENOLS

Disciplines:Cardiac and vascular medicine, Drug discovery and development, Medicinal products, Pharmaceutics, Pharmacognosy and phytochemistry, Pharmacology, Pharmacotherapy, Other pharmaceutical sciences, Nutraceuticals