Release of superoxide radicals by mouse macrophages stimulated by oxidative modification of glycated low density lipoproteins

Abstract

Diabetic patients have high levels of glycated LDL. Although glycated LDLs are implicated in the development of atherosclerosis in such patients, convincing data are lacking. We observed release of superoxide radicals (O 2 −) from mouse resident peritoneal macrophages stimulated by an oxidized/glycated LDL by using a highly sensitive and specific chemiluminescence method. Oxidized/glycated LDL was achieved by an addition of low concentration of Fe 3+ to glycated LDL. Macrophages took up an appreciable amount of the glycated LDL oxidized by iron, leading to the development of foam cells, while they did not take up untreated glycated LDL or the native LDL. These observations clearly indicate that the oxidized/glycated LDL reacts well with macrophages. Since an oxidation of glycated LDL may occur in vivo, the oxidized/glycated LDL might play an important role in atherogenesis.