title: Zinc nutrition and apoptosis of vascular endothelial cells: implications in atherosclerosis.
abstract: 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 that zinc requirements of the vascular endothelium are increased during inflammatory conditions such as atherosclerosis, where apoptotic cell death is also prevalent. Apoptosis is a morphologically distinct mechanism of programmed cell death which involves the activation of a cell-intrinsic suicide program, 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 derivatives, the endothelium is very susceptible to oxidative stress and to apoptotic injury mediated by blood lipid components, prooxidants, and cytokines. Thus, it is likely that the cellular lipid environment, primarily polyunsaturated fatty acids, can potentiate the overall endothelial cell injury by increasing cellular oxidative stress and cytokine release in proximity to the endothelium, which then could further induce apoptosis and disrupt endothelial barrier function. Our data suggest that zinc deficiency exacerbates the detrimental effects of specific fatty acids (e.g., linoleic acid) and inflammatory cytokines, such as TNF, on vascular endothelial functions. We propose that a major mechanism of zinc protection against disruption of endothelial cell integrity during inflammatory conditions, is by the ability of zinc to inhibit the pathways of signal transduction leading to apoptosis and especially mechanisms that lead to upregulation of caspase genes.
authors.affiliation: Department of Nutrition, University of Kentucky, Lexington 40506-0054, USA.
authors.forename: B
authors.initials: B
authors.lastname: Hennig
authors.forename: P
authors.initials: P
authors.lastname: Meerarani
authors.forename: P
authors.initials: P
authors.lastname: Ramadass
authors.forename: M
authors.initials: M
authors.lastname: Toborek
authors.forename: A
authors.initials: A
authors.lastname: Malecki
authors.forename: R
authors.initials: R
authors.lastname: Slim
authors.forename: C J
authors.initials: CJ
authors.lastname: McClain
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D001161:Arteriosclerosis / Q000473:pathology*; D004730:Endothelium, Vascular / Q000473:pathology*; D006801:Humans; D009752:Nutritional Status; D018384:Oxidative Stress; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D015032:Zinc / Q000502:physiology*
chemical_list: D000975:Antioxidants; D014409:Tumor Necrosis Factor-alpha; D015032:Zinc