Increased oxidative stress levels and normal antioxidant enzyme activity in circulating mononuclear cells from patients of familial hypercholesterolemia

Abstract

Familial hypercholesterolemia (FH) is a clinical condition with high risk for developing atherosclerosis. Increased oxidative stress (OS) and FH have been related to atherosclerosis, but no data are available on levels of OS and antioxidant enzyme activity in circulating mononuclear cells (CMCs) from FH patients. Circulating mononuclear cells are important mediators in atherosclerosis development, and chronically increased blood OS present in FH can induce modification in CMC activity. The objective of the study was to analyze the OS levels in CMCs from FH patients and controls. We have selected 30 nonrelated FH index patients and 30 normoglycemic and normocholesterolemic controls matched by age, sex, body mass index, abdominal circumference, and homeostasis model assessment index. Production of free radicals was analyzed by measurement of xanthine oxidase activity in plasma, reduced and oxidized glutathione (GSH and GSSG, respectively), and malonyldialdehyde in levels CMCs. Antioxidant status was analyzed by measuring antioxidant enzyme activity as superoxide dismutase, catalase, and glutathione peroxidase. We have found that FH patients showed significantly higher xanthine oxidase and malonyldialdehyde enzyme activities, as well as increased GSSG and lower GSH values resulting in a higher GSSG/GSH ratio. These data indicate a higher free radical production in plasma and increased OS levels in CMCs from patients than from controls. No significant differences were found in superoxide dismutase, catalase, and glutathione peroxidase activities between both groups. These data show an important alteration of OS regulation in FH and the absence of antioxidant response in CMCs mediated by some of the major antioxidant enzymes.