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High levels of testosterone (Testo) are associated with cardiovascular risk by increasing reactive oxygen species (ROS) formation. NADPH oxidases (NOX) are the major source of ROS in the vasculature of cardiovascular diseases. NOX4 is a unique isotype, which produces hydrogen peroxide (H2O2), and its participation in cardiovascular biology is controversial. So far, it is unclear whether NOX4 protects from Testo-induced endothelial injury. Thus, we hypothesized that supraphysiological levels of Testo induce endothelial NOX4 expression to attenuate endothelial injury. Human mesenteric vascular endothelial cells (HMECs) and human umbilical vein endothelial cells (HUVEC) were treated with Testo (10-7 M) with or without a NOX4 inhibitor [GLX351322 (10-4 M)] or NOX4 siRNA. In vivo, 10-wk-old C57Bl/6J male mice were treated with Testo (10 mg/kg) for 30 days to study endothelial function. Testo increased mRNA and protein levels of NOX4 in HMECs and HUVECs. Testo increased superoxide anion (O2 -) and H2O2 production, which were abolished by NOX1 and NOX4 inhibition, respectively. Testo also attenuated bradykinin-induced NO production, which was further impaired by NOX4 inhibition. In vivo, Testo decreased H2O2 production in aortic segments and triggered endothelial dysfunction [decreased relaxation to acetylcholine (ACh)], which was further impaired by GLX351322 and by a superoxide dismutase and catalase mimetic (EUK134). Finally, Testo led to a dysregulated endothelial cell migration, which was exacerbated by GLX351322. These data indicate that supraphysiological levels of Testo increase the endothelial expression and activity of NOX4 to counterbalance the deleterious effects caused by Testo in endothelial function. NEW & NOTEWORTHY By inducing ROS formation, high levels of testosterone play a major role in the pathogenesis of cardiovascular disease. NOXs are the major sources of ROS in the vasculature of cardiovascular diseases. Herein, we describe a novel compensatory mechanism by showing that NOX4 is a protective oxidant enzyme and counterbalances the deleterious effects of testosterone in endothelial cells by modulating hydrogen peroxide formation. [ABSTRACT FROM AUTHOR]

Purpose: Sedentary behavior (SB) has been shown to be associated with unhealthy outcomes in children, and it is not clear whether children living with human immunodeficiency virus (HIV) engage in different patterns of SB compared with healthy children. This cross-sectional study aimed to compare patterns of SB between children living with HIV and a healthy control group. Methods: A group of children with HIV and a paired control group wore accelerometers for 1 week and answered a questionnaire with items related to television viewing habits and computer usage. Accelerometer-derived and self-reported SB were compared between children living with HIV and controls and between treatment-based and viral load subgroups. Results: A total of 130 children (of which 53% are girls with a mean age of 12.1 y) participated in the study with 65 in each group. Children in the control group exhibited significantly more objectively measured SB daily when compared with the HIV group (515 vs 490 min/d, respectively), but no differences were found between the treatment-based and viral load subgroups. Children with HIV watched more television on weekdays, compared with the control group (P <.05). No other differences were found in comparisons of self-reported SB between the control and HIV and the treatment-based or viral load subgroups. Conclusion: Children living with HIV spend less time being sedentary than those in the healthy control group. Future studies are important for clarifying the causes and consequences of these differences. [ABSTRACT FROM AUTHOR]