Zinc nutrition and apoptosis of vascular endothelial cells: Implications in atherosclerosis

Little is known about the requirements and function of zinc in maintaining endothelial cell integrity, especially during stressful conditions, such as the inflammatory response in cardiovascular disease. There is evidence tha t zinc requirements of the vascular endothelium are increased during inflam matory conditions such as atherosclerosis, where apoptotic cell death is al so prevalent. Apoptosis is a morphologically distinct mechanism of programm ed cell death which involves the activation of a cell-intrinsic suicide pro gram, and there is evidence that factors such as inflammatory cytokines (e. g., tumor necrosis factor [TNF]) and pure or oxidized Lipids are necessary to induce the cell death pathway, Because of its constant exposure to blood components, including prooxidants, diet-derived fats, and their derivative s, the endothelium is very susceptible to oxidative stress and to apoptotic injury mediated by blood lipid components, prooxidants, and cytokines, Thu s, it is likely that the cellular lipid environment, primarily polyunsatura ted fatty acids, can potentiate the overall endothelial cell injury by incr easing cellular oxidative stress and cytokine release in proximity to the e ndothelium, which then could further induce apoptosis and disrupt endotheli al barrier function. Our data suggest that zinc deficiency exacerbates the detrimental effects of specific fatty acids (e.g., linoleic acid) and infla mmatory cytokines, such as TNF, on vascular endothelial functions. We propo se that a major mechanism of zinc protection against disruption of endothel ial cell integrity during inflammatory conditions, is by the ability of zin c to inhibit the pathways of signal transduction leading to apoptosis and e specially mechanisms that lead to upregulation of caspase genes. Nutrition 1999;15:744-748. (C) Elsevier Science Inc. 1999.