Copper deficiency and cardiovascular disease: role of peroxidation, glycation, and nitration.
Dietary copper deficiency causes a variety of cardiovascular deficits. Systemic effects include high blood pressure, enhancement of inflammation, anemia, reduced blood clotting, and possibly arteriosclerosis. Effects on specific organs or tissues include weakened structural integrity of the heart and blood vessels, impairment of energy use by the heart, reduced ability of the heart to contract, altered ability of blood vessels to control their diameter and grow, and altered structure and function of circulating blood cells. In some instances, the cause of a defect can be directly attributed to reduced activity of a specific copper-dependent enzyme. However, three nonspecific mechanisms of damage have been implicated in cardiovascular defects of copper deficiency. They are peroxidation, the interaction of oxygen-derived free radicals with lipids and proteins (possibly DNA); glycation, the nonenzymatic glycosylation of proteins; and nitration, the interaction of nitric oxide and its metabolites with peptides and proteins. Though independently these mechanisms present great potential for damage, the possibility that they may interact presents an added reason for concern. Furthermore, the fact that at least two of these mechanisms are associated with diabetes and aging suggests that copper deficiency may exacerbate deficits associated with these two conditions.
Saari
J T
JT
U.S. Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, ND 58202, USA. jsaari@gfhnrc.ars.usda.gov
D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism*; D003300:Copper / Q000172:deficiency*; D005609:Free Radicals / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II
D005609:Free Radicals; D017127:Glycation End Products, Advanced; D009569:Nitric Oxide; D003300:Copper; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II