Response to Endothelial Dysfunction, Isoprostanes, and Copper Deficiency
We appreciate Klevay’s comments1 regarding the potential role of copper supplement for the treatment of endothelial dysfunction. Our study focused on the association among coronary endothelial dysfunction, local bioavailability of NO, and local reactive oxygen species generation.2 We demonstrated that, in patients with endothelial dysfunction, there is increased local ROS generation, reduced activity of antioxidants (superoxide dismutase) and preserved production of NO. However, there was no significant difference in the arterial levels of either isoprostanes or superoxide dismutase between patients with coronary endothelial dysfunction and patients with normal response to acetylcholine. The relationship among copper deficiency, isoprostanes, superoxide dismutase, and arterial response to acetylcholine3 is indeed very intriguing. Thus, it may be speculated that the relative deficiency of copper as a central molecule in the antioxidant axis may play a role in the mechanism of endothelial dysfunction.
It should be noted that, although copper deficiency may have adverse effects on the cardiovascular system, high copper levels are associated with increased risk of death from cardiovascular disease. In fact, even the second quartile of copper was associated with a trend toward increased risk compared with the lowest quartile (hazard ratio: 1.84).4 Increased copper levels were also an independent predictor for acute myocardial infarction.5
The use of copper in medicine dates to Hippocrates, but there are not much data to support its use in cardiovascular disease. The effect of antioxidants on endothelial function should be studied. Copper, an antioxidant nutrient, would be a potential agent.
Sources of Funding
This study was supported by NIH grants K24, HL-69840, and R01 HL-63911 and the Mayo Foundation.
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