Oxidized Extracellular DNA Suppresses Nitric Oxide Production by Endothelial NO Synthase (eNOS) in Human Endothelial Cells (HUVEC)

Circulating DNA from patients with cardiovascular diseases reduce the synthesis of NO in endothelial cells, which is probably related to oxidative modifi cation of DNA. To test this hypothesis, HUVEC cells were cultured in the presence of DNA containing similar to 1 (nonoxidized DNA), 700, or 2100 8-oxodG/106 nucleosides. Nonoxidized DNA stimulated the synthesis of NO, which was associated with an increase in the expression of endothelial NO synthase. Oxidized NO decreased the amount of mRNA and protein for endothelial NO synthase, but increased the relative content of its low active form. These changes were accompanied by reduction of NO production. These fi ndings suggest that oxidative modifi cation of circulating extracellular DNA contributes to endothelial dysfunction manifested in suppression of NO production.