Nutrition and endothelial cell function: Implications in atherosclerosis

Nutrient-mediated functional changes of the endothelium and the underlying tissues may be significantly involved in disease processes, such as atherosclerosis. Endothelial cells interact with blood components and the abluminal tissues, thus playing an active role in many aspects of vascular function. There is evidence that individual nutrients or nutrient derivatives may either provoke or prevent metabolic and physiologic perturbations of the vascular endothelium. Diets high in fat and/or calories are considered a risk factor for the development of atherosclerosis because of excessive free fatty acid release as a result of hydrolysis of triglyceride-rich lipoproteins. It has been hypothesized that high levels of diet-derived fatty acids can cause endothelial cell activation or dysfunction. Our research has shown that certain unsaturated fatty acids and their derivatives can disrupt normal endothelial integrity, thus reducing the ability of the endothelium to act as a selectively permeable barrier to blood components. Mechanisms underlying fatty acid-mediated endothelial cell dysfunction may be related to changes in fatty acid composition as well as to an increase in cellular oxidative stress. Selective lipid accumulation and fatty acid changes in endothelial cells can modulate signal transduction mechanisms and inflammatory mediators. An imbalance in cellular oxidative stress/antioxidant status mediated by dietary fats rich in certain unsaturated fatty acids 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 intensify an inflammatory response in atherosclerosis. Our data also suggest that certain nutrients, which have antioxidant and/or membrane stabilizing properties, can protect endothelial cells by interfering with lipid/cytokine-mediated endothelial cell dysfunction. These findings contribute 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.