Role of oxidative stress in the pathogenesis of abdominal aortic aneurysms.
The role of inflammation in the pathogenesis of abdominal aortic aneurysms (AAA) is well established. The inflammatory process leads to protease-mediated degradation of the extracellular matrix and apoptosis of smooth muscle cells (SMC), which are the predominant matrix synthesizing cells of the vascular wall. These processes act in concert to progressively weaken the aortic wall, resulting in dilatation and aneurysm formation. Oxidative stress is invariably increased in, and contributes importantly to, the pathophysiology of inflammation. Moreover, reactive oxygen species (ROS) play a key role in regulation of matrix metalloproteinases and induction of SMC apoptosis. ROS may also contribute to the pathogenesis of hypertension, a risk factor for AAA. Emerging evidence suggests that ROS and reactive nitrogen species (RNS) are associated with AAA formation in animal models and in humans. Although experimental data are limited, several studies suggest that modulation of ROS production or activity may suppress AAA formation and improve experimental outcome in rodent models. Although a number of enzymes can produce injurious ROS in the vasculature, increasing evidence points toward a role for NADPH oxidase as a source of oxidative stress in the pathogenesis of AAA.
McCormick
Michael L
ML
Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, USA.
Gavrila
Dan
D
Weintraub
Neal L
NL
D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000503:physiopathology*; D017209:Apoptosis; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012680:Sensitivity and Specificity
D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; D020782:Matrix Metalloproteinases