Influence of nutrients and cytokines on endothelial cell metabolism

The vascular endothelium plays an active role in physiological processes such as hemostasis, regulation of vessel tone and vascular permeability. Cell injury, or any event which disrupts endothelial integrity and thus endothelial permeability properties, may be involved in the early events leading to atherosclerotic lesion formation. Because of its constant exposure to blood components, including prooxidants, diet-derived fats and their derivatives, the endothelium is susceptible to oxidative stress and to injury mediated by blood lipid components. It is likely that these events potentiate the overall inflammatory response to injury by increasing cytokine release in proximity to the endothelium, which then could further disrupt endothelial barrier function. Even though mechanisms associated with lipid/cytokine-mediated endothelial cell dysfunction are unclear, our data suggest that they may be both oxidative and non-oxidative in nature. We suggest that dietary fats, rich in certain unsaturated fatty acids are atherogenic by enhancing the formation of reactive oxygen intermediates. These intermediates can activate oxidative stress-responsive transcription factors, such as NF-kB, which in turn may promote cytokine production, adhesion molecule expression and ultimately endothelial barrier dysfunction. The resulting disturbances in endothelial integrity possibly allow increased penetration of cholesterol-rich lipoprotein remnants into the arterial wall, a critical event in the etiology of atherosclerosis. Data suggest that certain nutrients, which have antioxidant and/or membrane stabilizing properties, protect endothelial cells by interfering with the above proposed mechanisms of endothelial cell dysfunction.