Battelli Maria Giulia, Polito Letizia, Bolognesi Andrea
Alma Mater Studiorum University of Bologna, Department of Experimental, Diagnostic and Specialty Medicine - DIMES, General Pathology Unit, Via S. Giacomo 14, 40126 Bologna, Italy.
Atherosclerosis. 2014 Dec;237(2):562-7. doi: 10.1016/j.atherosclerosis.2014.10.006. Epub 2014 Oct 17.
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.
内皮黄嘌呤氧化还原酶（XOR）与NAD（P）H氧化酶和一氧化氮（NO）合酶一起在炎症信号传导、NO生成调节和血管功能中发挥生理作用。这些酶产生的氧化应激可能会导致内皮功能障碍，进而引发动脉粥样硬化、心血管疾病和代谢综合征。XOR活性产生的氧化产物和抗氧化产物都与高血压、吸烟导致的血管损伤、血脂异常和糖尿病的发生有关，而这些都是动脉粥样硬化的主要危险因素。特别是，尿酸在血管改变中可能具有保护作用和有害作用，因此说明了XOR抑制的多向效应。此外，XOR产物与细胞分化有关，导致脂肪生成和泡沫细胞形成，以及动脉平滑肌细胞在增殖和迁移后产生单核细胞趋化蛋白-1。XOR在脂肪生成中的作用还与胰岛素抵抗和肥胖有关，这是2型糖尿病的两个主要特征。
