Reactive oxygen species and vascular cell apoptosis in response to angiotensin II and pro-atherosclerotic factors

Reactive oxygen species (ROS) are known to induce apoptotic cell death in v arious cell types. In the vessel wall, ROS can be formed by macrophages wit hin the atherosclerotic plaque or can act on the endothelium after adhesion of monocytes or leucocytes. Moreover, ROS are endogenously synthesized by endothelial and vascular smooth muscle cells by NAD(P)H oxidase. Enhanced R OS production is a very early hallmark in the atherogenic process, suggesti ng a link between ROS and apoptosis. In endothelial cells, the endogenous g eneration of ROS is induced by different pro-inflammatory and pro-atheroscl erotic factors such as Ang II, oxLDL or TNF alpha, which all promote the ex ecution of programmed cell death. ROS synthesis is thereby causally involve d in apoptosis induction, because antioxidants prevent endothelial cell dea th. The pro-apoptotic effects of endogenous ROS in endothelial cells mechan istically seems to involve the disturbance of mitochondrial membrane permea bility followed by cytochrome c release, which finally activates the execut ioner caspases. In contrast to the pro-apoptotic capacity of ROS in endothe lial cells, in vascular smooth muscle cells emerging evidence suggests that endogenous ROS synthesis promotes cell proliferation and hypertrophy and d oes not affect cell survival. However, high concentrations of exogenous ROS can also stimulate smooth muscle cell apoptosis as shown for other cell ty pes probably via activation of p53. Taken together, the double-edged effect s of endogenously derived ROS in endothelial cells versus VSMC may provide a mechanistic clue to the anti-atherosclerotic effects of antioxidants show n in experimental studies, given that the promotion of endothelial survival in combination with inhibition of VSMC proliferation blocks two very impor tant seeps in the pathogenesis of atherosclerosis. (C) 2000 Elsevier Scienc e B.V. All rights reserved.