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Monocyte NADPH Oxidase Subunit p22^phox and Inducible Hemeoxygenase-1 Gene Expressions Are Increased in Type II Diabetic Patients: Relationship with Oxidative Stress

Department of Clinical and Experimental Medicine, University of Padova, 35128 Padova, Italy

Address all correspondence and requests for reprints to: Angelo Avogaro, M.D., Department of Clinical and Experimental Medicine, University of Padova, School of Medicine, Via Giustiniani 2, 35128 Padova, Italy. E-mail: angelo.avogaro{at}unipd.it.

Oxidative stress is associated with diabetes mellitus: a role of vascular NADPH oxidase as a source of superoxide has been demonstrated. We determined whether in type 2 diabetes mononuclear cells, NADPH oxidase and the inducible hemeoxygenase (HO-1) gene expressions are activated. In monocytes from 25 outpatients with type 2 diabetes, p22^phox gene expression was higher (0.71 ± 0.09 p22^phox/ß-actin gene expression ratio) than that observed in 19 controls (0.56 ± 0.09, P < 0.001). Similarly, HO-1 gene expression was significantly higher in diabetic patients (0.77 ± 0.12 HO-1/ß-actin gene expression ratio) than in controls (0.41 ± 0.14, P < 0.001). The p22^phox and HO-1 gene expressions were also determined during (plasma glucose 363 ± 40 mg/dl) and after (125 ± 11 mg/dl) metabolic decompensation in 10 type 2 diabetic patients. The correction of the metabolic milieu was associated with a 19% ± 3% (P < 0.01) and 30% ± 3% (P < 0.01) decrease in the p22^phox and HO-1 gene expressions, respectively. In a multivariate analysis, age was independently associated to p22^phox gene expression in circulating monocytes in type 2 diabetics [13% (adjusted R²), P < 0.05]. Decompensated type 2 diabetes is associated with increased p22^phox and HO-1 gene expressions in circulating monocytes; the metabolic normalization reduces but does not normalize this activation. These findings suggest that these cells, which play a crucial role in the earliest events of atherosclerotic lesion, are subjected to an increased oxidative stress.

Abbreviations: GAPDH, Glyceraldehyde-3-phosphate dehydrogenase; HbA1c, hemoglobin A1c; HDL, high-density lipoprotein; HO-1, hemeoxygenase; NAD(P)H, nicotinamide adenine dinucleotide phosphate; ROS, reactive oxygen species.

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