FIG. 1.
Hypothesized contributions from Nox2-generated oxidative stress to the process of atherosclerosis. When NADPH donates electrons to molecular oxygen via Nox2, O2·− generation occurs. Oxidative stress occurs when O2·− production exceeds the antioxidant capacity of the immediate environment. Oxidative stress can contribute to atherosclerosis progression by various mechanisms (7). ↑, increase; ↓, decrease. Mice with endothelial cell–specific insulin resistance (ESMIRO and IR+/− mice) exhibit increased Nox2-mediated O2·− generation to an extent that evokes endothelial dysfunction. Treatment of ESMIRO and IR+/− mice with the Nox inhibitor gp91ds-tat (+gp91ds-tat) or endothelial cell–specific knockout of Nox2 in ESMIRO mice (ESMIRO / Nox2y/−) reduces O2·− production and restores endothelial function. *Endothelial function was assessed in the current study (3), but the influence of endothelial cell–specific Nox2 deletion on other potential contributors to atherosclerosis depicted in the figure has not been investigated. VSMC, vascular smooth muscle cell; MMPs, matrix metalloproteinases.