Abstract

The vascular endothelium synthesizes pro- and anti-oxidant proteins that influence the susceptibility of the vascular wall to atherosclerosis. Cardiovascular risk factors such as obesity may alter vascular endothelial cell protein expression (VECPE), thus increasing vulnerability to atherosclerosis. Sex-independent relations between total and abdominal fat and VECPE (quantitative immunofluorescence analysis of venous endothelial cells) were determined in 122 men and women free of clinical disease (age: 41±2 [mean±SE], range 18–73 yr; body mass index [BMI]: 25.6 ± 0.4, 18.4–36.7 kg/m2; total body fat [TBF]: 23.0±1.0, 4.1–55.0 kg; waist circumference [WC]: 85.4±1.2, 63.0–122.9 cm). BMI, TBF and WC were positively associated with VECPE of the oxidant enzyme NADPH oxidase-p47 (part correlation coefficient: 0.22–0.24, P≤ 0.04) and the antioxidant enzyme catalase (0.71–0.75, P<0.0001). TBF was positively associated with VCEPE of nitrotyrosine (0.36, P=0.003), a marker of oxidative protein damage. Overweight/obese subjects (BMI ≥25) had 35–129% higher VECPE of NADPH oxidase-p47, catalase, nitrotyrosine, and the antioxidant CuZn superoxide dismutase than non-overweight/obese subjects (P ≤ 0.04). In adult humans, elevated body fatness is associated with a pro-oxidant vascular endothelial phenotype featuring a compensatory up-regulation of antioxidant enzymes. Supported by NIH AG006537, AG013038, AG022241, AG20683, RR00051.

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