Thiocyanate catalyzes myeloperoxidase-initiated lipid oxidation in LDL

There is evidence that LDL oxidation may render the lipoprotein atherogenic. The myeloperoxidase–hydrogen peroxide (MPO/H2O2) system of activated phagocytes may be involved in this process. Chloride is supposed to be the major substrate for MPO, generating reactive hypochlorous acid (HOCl), modifying LDL. The pseudo-halide thiocyanate (SCN−) has been shown to be a suitable substrate for MPO, forming reactive HOSCN/SCN•. As relatively abundant levels of SCN− are found in plasma of smokers—a well-known risk group for cardiovascular disease—the ability of SCN− to act as a catalyst of LDL atherogenic modification by MPO/H2O2 was tested. Measurement of conjugated diene and lipid hydroperoxide formation in LDL preparations exposed to MPO/H2O2 revealed that SCN− catalyzed lipid oxidation in LDL. Chloride did not diminish the effect of SCN− on lipid oxidation. Surprisingly, SCN inhibited the HOCl-mediated apoprotein modification in LDL. Nitrite—recently found to be a substrate for MPO—showed some competing properties. MPO-mediated lipid oxidation was inhibited by heme poisons (azide, cyanide) and catalase. Ascorbic acid was the most effective compound in inhibiting the SCN−-catalyzed reaction. Bilirubin showed some action, whereas tocopherol was ineffective. When LDL oxidation was performed with activated human neutrophils, which employ the MPO pathway, SCN− catalyzed the cell-mediated LDL oxidation. The MPO/H2O2/SCN− system may have the potential to play a significant role in the oxidative modification of LDL—an observation further pointing to the link between the long-recognized risk factors of atherosclerosis: elevated levels of LDL and smoking.