Endothelial NADPH oxidase 2: when does it matter in atherosclerosis?

This editorial refers to ‘Endothelial-specific Nox2 overexpression increases vascular superoxide and macrophage recruitment in ApoE−/− mice’ by G. Douglas et al ., pp. 20–29, this issue. Reactive oxygen species (ROS) act as a double-edged sword in numerous cardiovascular conditions. In addition to their known detrimental effects on all cellular macromolecules, referred to as oxidative stress , lower amounts of ROS also directly modify molecules and thereby modulate their functions - this process has been termed redox signalling . Both oxidative stress and redox signalling have been implicated in the process of atherosclerosis. The sources of cellular ROS include mitochondria, NADPH oxidases (Noxs), dysfunctional nitric oxide synthases, xanthine oxidase, and other oxygenases. Among these, the Noxs are unique, since their primary function is to produce ROS.1 The Nox family comprises seven members, Nox1–5 and DUOX1–2, each based on a distinct core catalytic subunit.1,2 Nox1, 2, 4, and 5 are expressed in cardiovascular cells, although Nox5 is only found in humans and not in rodents.3 An involvement of Nox2 in atherosclerosis has been suspected. It was the first NADPH oxidase to be identified and is responsible for the phagocytic oxidative burst of neutrophils. It has subsequently been found to be expressed at lower levels in endothelial cells, cardiomyocytes, fibroblasts, vascular smooth muscle cells, monocytes, and macrophages, the latter two being central …