Endothelial lipid storage and its impact on endothelial metabolism and functions

Endothelial cells constitute the inner monolayer of all vessels. They share many critical functions for tissue perfusion. They mainly participate in the maintenance of vascular homeostasis through the release of different active metabolites, such as nitric oxide. The endothelium as a whole, by performing these vital functions, should be considered as an active organ. Although only partly dependent on lipids for their metabolism, endothelial cells have developed the ability to store fatty acids in the form of lipid droplets. Their role is assumed to protect the underlying tissues as well as the endothelial cells themselves from any possible lipotoxicity, in the case of recurrent surges of free fatty acid concentration in the bloodstream. Like all peripheral organs, the metabolism of the endothelium (including lipid metabolism) is partially regulated by circadian genes, whose expression varies throughout the day, in an approximately 24 hours cycle, thanks to combined influences of the central and peripheral circadian clocks. In this work, we are developing an in vitro model that will allow us to study the impact of saturated, monounsaturated and polyunsaturated fatty acid storage on endothelial functions and metabolism. Endothelial endogenous circadian rhythm has been added as a variable to match as close as possible the in vivo conditions. We started by analyzing the expression of clock genes and proteins. We then monitored the accumulation of fatty acids (as lipid droplets) in endothelial cells over time. Our results demonstrate difference in the uptake according to the nature, concentration and duration of exposure to different fatty acids. To go further in the study of lipid storage in endothelial cells, we started to apply the Nanolive technology to our protocol. We then plan to assess how this lipid accumulation changes when we couple lipid exposure to circadian rhythms. Then, we will study how lipid accumulation affects endothelial function, metabolism and protective capacity against lipotoxicity.