Xanthine oxidoreductase in atherosclerosis pathogenesis: Not only oxidative stress

Abstract

Endothelial xanthine oxidoreductase (XOR) together with NAD(P)H oxidase and nitric oxide (NO) synthase plays a physiologic role in inflammatory signalling, the regulation of NO production and vascular function. The oxidative stress generated by these enzymes may induce endothelial dysfunction, leading to atherosclerosis, cardiovascular diseases and metabolic syndrome. XOR activity creates both oxidant and anti-oxidant products that are implicated in the development of hypertension, smoking vascular injury, dyslipidemia and diabetes, which are the main risk factors of atherosclerosis. In particular, uric acid may have a protective as well as a detrimental role in vascular alterations, thus justifying the multi-directional effects of XOR inhibition. Moreover, XOR products are associated with cell differentiation, leading to adipogenesis and foam cell formation, as well as to the production of monocyte chemoattractant protein-1 from arterial smooth muscle cells, after proliferation and migration. The role of XOR in adipogenesis is also connected with insulin resistance and obesity, two main features of type 2 diabetes.

Resveratrol ameliorates high glucose-induced oxidative stress injury in human umbilical vein endothelial cells by activating AMPK

“…Oxidative stress, reflected by increased cellular oxidation reactions and decreased reduction reactions (Banerjee and Vats, 2013), has a close relationship with HG-induced vascular injury (Battelli et al , 2014, Menini et al , 2014, Thallas-Bonke et al , 2014.…”

Reactive Oxygen Species Generation and Atherosclerosis

“…Major ROS include superoxide (O 2 · − ) and hydroxyl (HO·) free radicals, as well as nonradical molecules, such as hydrogen peroxide (H 2 O 2 ). Primary sources of oxidative stress in vessel wall are mitochondria, 18 uncoupled nitric oxide synthase, 19 lipoxygenase, 20 myeloperoxidase, 21 xanthine oxidase (XO), 22 and importantly NAD(P)H oxidases 23 ( Figure 1). However, the influence of ROS-producing enzymes, especially NADPH oxidases, in the development of atherosclerosis is ambiguous.…”

Inflammation and Oxidative Stress: Critical Role for Metabolic Syndrome

“…Uric acid may have a protective as well as a detrimental role in vascular alterations, thus justifying the multi-directional effects of xantine oxidoreductase (XOR) inhibition. Moreover, XOR products are associated with cell differentiation, leading to adipogenesis and foam cell formation, as well as to the production of monocyte chemoattractant protein-1 from arterial smooth muscle cells, after proliferation and migration; the role of XOR in adipogenesis is also connected with insulin resistance and obesity, two main features of type 2 diabetes [28]. Hyperglycemia-induced oxidative damage in adipocytes and its potential links to diabetes progression when advanced glycation endproducts (AGEs) -especially glycated albumin formation is increased [29].…”