NUTRITIONAL IMPLICATIONS IN VASCULAR ENDOTHELIAL-CELL METABOLISM

Endothelial cells interact with blood components and the albuminal tis sues, thus playing an active role in many aspects of vascular function . Numerous physiologic and pathophysiologic stimuli are often mediated by nutrients that can contribute to the overall functions of endothel ial cells in the regulation of vascular tone, coagulation, cellular gr owth, immune and inflammatory responses. Therefore, nutrient-mediated functional changes of the endothelium and the underlying tissues may b e significantly involved in disease processes such as atherosclerosis. There is evidence that individual nutrients or nutrient derivatives m ay either provoke or prevent metabolic and physiologic perturbations o f the vascular endothelium. Diets high in fat and/or calories are cons idered a risk factor for the development of atherosclerosis. Our resea rch has shown that certain diet-derived lipids and their derivatives c an disrupt normal endothelial integrity, thus reducing the ability of the endothelium to act as a selectively permeable barrier to blood com ponents. Mechanisms underlying fatty acid-mediated endothelial cell dy sfunction may be related to changes in fatty acid composition as well as to an increase in cellular oxidative stress. Selective Lipid accumu lation and fatty acid changes in endothelial cells can modulate membra ne fluidity, proteoglycan metabolism and signal transduction mechanism s. Most importantly, dietary fats rich in certain unsaturated fatty ac ids, may be atherogenic by enhancing the formation of reactive oxygen intermediates. A subsequent imbalance in cellular oxidative stress/ant ioxidant status can activate oxidative stress-responsive transcription factors, which in turn may promote cytokine production, expression of adhesion molecules on the surface of endothelial cells, and thus inte nsify an inflammatory response in atherosclerosis. Our data also sugge st that certain nutrients, which have antioxidant and/or membrane stab ilizing properties, can protect endothelial cells by interfering with lipid/cytokine-mediated endothelial cell dysfunction. These findings c ontribute to the understanding of the interactive role of dietary fats with inflammatory components, as well as with nutrients that exhibit antiatherogenic properties, in the development of atherosclerosis.