CONICET | Buscador de Institutos y Recursos Humanos

Excessive production of reactive oxygen species (ROS) plays a detrimental role in the progression of atherosclerosis. Increased expression of the pro-oxidant enzyme NADPH oxidase (NOX) in the arterial wall has been hypothesized to correlate with vascular injury and progression of atheroma plaque. Since the gene encoding NOX5 is not expressed in the mouse genome, we examined the expression of NOX5 isoform in human endothelial cells (HUVECs) under pro-atherogenic and pro-inflammatory conditions. HUVECs were exposed to Angiotensin II (AngII) or to tumor necrosis factor (TNF-alpha) and incubated with selective NOX-inhibitors one hour prior treatment. NOX expression was determined by qRT-PCR and oxidative stress was evaluated using a fluorescent probe sensitive to ROS production. HUVECs expressed both NOX2 and NOX5 mRNA (2.4 ΔCT ±0.1 and 19.5 ΔCT ±1.8, respectively). AngII and TNF-alfa increased ROS generation in HUVECs which was inhibited by selective inactivation of NOX2 or NOX5. As enhanced activity of NOXs occur in many pathological conditions including hypertension and heart failure we next determined the expression of NOX in Human Mammary Arteries (HMA) of patients undergoing coronary bypass surgery. NOX2 and NOX5 expression in HMA were similar (7.42 ΔCT ± 0.55; and 8.32 ΔCT ± 0.43, respectively), and they exhibited a positive and significant correlation (r= 0.665; p=0.0007) between them. High NOX5 expression was found in patients with Hypertension, Dyslipidemia and Obesity. Our results suggest that NOX2 and NOX5 are up-regulated in pro-atherogenic conditions and contribute to endothelial dysfunction. Taking these results into account, it is attractive to speculate that small, selective and specific inhibitory molecules of different NOXs could exert a beneficial effect on vascular pathology