The association between marginal zinc deficiency and cardiovascular disease has been reported in the literature, but the exact mechanisms of action are unknown. One hypothesis suggests that marginal zinc deficiency causes an increase in oxidative stress that results in vascular dysfunction and inflammation. Researchers1 investigating marginal zinc deficiency and vascular dysfunction function have tested this hypothesis in cultured endothelial cells and found that zinc deficient cells displayed oxidative stress, which was subsequently decreased by zinc supplementation. Similarly, NF-κβ DNA binding activity (which controls DNA transcription in response to cytokines), and COX-2 and E-selectin gene expression (coding for a pro-inflammatory enzyme and a cell adhesion molecule, respectively) was markedly increased during zinc deficiency, but this reversed upon zinc supplementation. Zinc deficiency also down-regulated peroxisome proliferator-activated receptor alpha PPARα, which may be required to inhibit NF-κβ signalling.
These results suggest that marginal zinc deficiency may produce oxidative stress that adversely affects the physiology of endothelial cells, leading to vascular dysfunction. That the inflammatory response was caused by a zinc deficiency was supported my mouse experiments that showed systemic inflammation with low zinc intakes. The balance between NF-κβ and PPARα signalling might be critical in regulating inflammatory diseases. Down-regulation of PPARα and upregulation of NF-κβ may increase gene expression of pro-inflammatory markers such as COX-2 and activators of immune response such as E-selectin. E-selectin plays a role in recruiting leukocytes to the point of injury and may therefore be involved in the development of atherosclerosis through the influx of white blood cells to the inflamed artery lining. The COX-2 enzyme system is responsible for production of prostaglandin E2, an inflammatory hormone synthesised from arachidonic acid present in the cell membranes.
Adequate zinc intake as part of a high quality diet may therefore play a role in the prevention of cardiovascular disease. Care should always be taken when assessing results from in vitro and animal model studies, but these data provide a mechanism which explains the association between zinc deficiency and cardiovascular disease. Dysfunction of the endothelial lining through diet induced oxidative stress is gaining traction as a possible cause of cardiovascular disease. Zinc is not the only nutrient that is required for correct function of the endothelium, but is one of a large number of nutrient factors that likely produce synergistic effects at maintaining the correct balance between pro- and anti-inflammatory action within this tissue. The fact that zinc has been identified as being deficient in a large proportion of Western diets is concerning given the high incidence of cardiovascular disease amongst these populations.
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