Nitrosylated Proteins in Monocytes as a new Marker of Oxidative-Nitrosative Stress in Diabetic Subjects with Macroangiopathy

Background: Peroxynitrite plays an important role in the pathogenesis of diabetic complications. Nitrosylated protein expression in peripheral blood monocytes reflects intracellular peroxynitrite injury, and thus could be a marker of higher diagnostic and prognostic value than plasma nitrotyrosine level. The purpose of this pilot study was to assess if peripheral blood monocytes of diabetic subjects accumulate nitrosylated proteins, and if nitrosylated protein expression correlates with blood glucose control, variables of lipid profile, C-reactive protein concentration (a marker of inflammation), and differs in patients with and without diabetic macrovascular and microvascular complications. Methods: Nitrosylated protein expression in peripheral blood monocytes (Western blot analysis) was assessed in 31 subjects with diabetes mellitus (29 Type 2, 2 Type 1; 20 males, 11 females; mean age 66 years). The presence of microangiopathy was defined by retinopathy, albumin excretion, and/or neuropathy, and macroangiopathy by carotid plaques, a history of myocardial infarction, and/or stroke. Results: Diabetic subjects accumulated significant amounts of nitrosylated proteins in peripheral blood monocytes. Nitrosylated protein expression positively correlated with body weight, blood glucose, HbA(1)C, and plasma C-reactive protein concentrations in the whole cohort as well as in subjects with diabetic macroangiopathy. Conclusions: Monocyte nitrosylated protein expression is a new biomarker of metabolic control and inflammation in diabetic subjects with macroangiopathy. A more detailed assessment of diabetic microvascular complications in a larger group of patients is needed to determine if this variable can be employed as a biomarker of the presence, severity, and progression of diabetic neuropathy, retinopathy, and nephropathy.