Editorial (Oxidative Stress in the Vascular Wall: A Useful Physiological Process or a Therapeutic Target in Vascular Disease?)

THE ROLE OF REDOX STATE IN VASCULAR FUNCTION During the last few years, the progress in molecular cardiology allowed the in-depth study of the mechanisms involved in atherogenesis [1]. Importantly, this is now considered to be an inflammatory disease that is highly regulated by complex biological networks inside the human vascular wall [1]. In these mechanisms, oxidative stress plays a central role [2]. Reactive oxygen species (ROS) such as superoxide anions (O2 -.), hydroxyl radicals (OH-), peroxynitrite (ONOO-), are molecules with important role in host defence mechanisms of the human immune system [3] and key signalling molecules involved in the physiology of the human vascular wall [4, 5]. SOURCES OF ROS IN THE VASCULAR WALL Vascular bioavailability is there if ROS is dependent on the balance between its biosynthetic rate by various enzymatic sources in the vascular wall (such as NADPH-oxidase, Nitric oxide synthases (NOSs), xanthine oxidase (XO), mitochondrial oxidases and others) and their “deactivation” by the endogenous antioxidant defence systems (such as superoxide dismutase, glutathione peroxidase, heme oxygenase, thioredoxin peroxidase/ peroxiredoxin, catalase and paraoxonase) [6]. When this balance is disturbed (e.g. in the presence of atherosclerosis risk factors such as hypertension, dyslipidaemia, smoking, obesity, etc), then these ROS trigger a number of pathophysiological processes that eventually lead to atherogenesis [6]. ROS induces the oxidation of LDL at the subendothelial space, resulting in the formation of oxidised LDL (ox-LDL). This is a highly proatherogenic molecule that induces the release of multiple chemotactic signalling mediators promoting migration of more monocytes to the sub-endothelial space. Eventually, ox-LDL is up-taken up by the resident macrophages leading to the formation of foam cells, that will form the lipid core of atheromatous plaque [7]. Importantly, ROS and ox-LDL activate a number of proinflammatory redox-sensitive transcriptional pathways (such as nuclear factor kappa B (NF-kappaB) and activating protein -1 (AP-1)), inducing the expression of various pro-atherogenic, pro-inflammatory genes and promoting atherogenesis [7]. A summary of these mechanisms is provided in the Fig. (1).