Increased Cellular and Circulating Biomarkers of Oxidative Stress in Nascent Metabolic Syndrome

Abstract

Metabolic syndrome (MetS) confers a greater risk for both cardiovascular disease (CVD) and diabetes. Oxidative stress (OS) could contribute to this excess risk. However, there are few data examining both cellular and circulating biomarkers of OS in MetS uncomplicated by diabetes and CVD. The aim of the study was to evaluate both cellular and circulating biomarkers of OS in MetS uncomplicated by diabetes or CVD. At an academic medical center, we compared MetS (n=43) vs. control subjects (n=33). Fasting blood was collected for monocyte isolation and assay of OS biomarkers. Monocyte nicotinamide adenine dinucleotide phosphate oxidase activity (p22 phox and p47), superoxide anion release, oxidized-low-density lipoprotein (Ox-LDL), nitrotyrosine, and nuclear factor erythroid 2-related factor were measured. There was significantly increased release of superoxide from the monocytes (basal and after activation) of MetS compared with controls adjusted for body mass index. Body mass index-adjusted plasma levels of Ox-LDL and nitrotyrosine were significantly increased in MetS. There was a linear trend between biomarkers of oxidative stress and increasing number of features of MetS. Also, there was a significant increase in nicotinamide adenine dinucleotide phosphate oxidase membrane expression of p22 phox and p47 phox in MetS. The major cellular antioxidant defense, nuclear factor erythroid 2-related factor was significantly decreased. There were significant correlations between homeostasis model assessment insulin resistance index and both Ox-LDL and nitrotyrosine and superoxide and Ox-LDL. Collectively, nascent MetS is associated with increased OS as evidenced by both circulating and cellular biomarkers, and this could contribute to the risk for both diabetes and CVD.