Endothelial dysfunction and nutraceutical approaches: In vitro system to study the modulation of metabolic markers on human aortic endothelial cells

Objective: Endothelial dysfunction (ED) includes both microvascular and macrovascular complications and is considered a hallmark in the patho-physiology of metabolic syndrome (MetS). ED is characterized by impaired endothelium-dependent relaxation, excessive cytokines production, release of inflammatory factors and oxidative stress. The aim of this work is to setup experimental strategies to study in vitro macrovascular endothelial damages related to MerS: the same protocols will be used to test the role of natural compounds with nutraceutical interest (Berberine (BBR) and red yeast rice (RYR)). Methods: Endothelial complications associated to MetS were assessed treating human aortic endothelial cells (HAEC) with uric acids (UA). leptin and low density lipoproteins (LDL). We analyzed the modulation of some metabolic and biochemical markers (lipid peroxidation, cholesterol determination. ROS production) or 1CAM-I and Carnitine Palmitoyltransferase 2 (CPT2) production. The in vitro model was used to quantitatively characterize the modulation of these markers by natural compounds usually introduced with diet (BBR and RYR). Results: UA (6. 9 and 12mg/dl) treatment reduced HAEC viability, increased ROS production and modified ICAM-I expression. The incubation with Leptin (lOOng/ml) increased CPT2 expression (24 h). Moreover, LDL (200 ng/ml) promoted lipid peroxidation and altered cholesterol production. BBR and RYR differently affected the markers. Incubation of HAEC with BBR modified the response to both UA and Leptin, and counteracted ROS production, lipid peroxidation and ICAM-1 or CFT2 expression. RYR was less effective than BBR. Conclusions: In this work we developed a new simplified in vitro system suitable to evaluate ED associated to MetS. Moreover, the same system was used to test the role of natural compounds with nutraceutical applications to evaluate their possible preventive effect on ED development.