Xanthine oxidoreductase: A leading actor in cardiovascular disease drama

Cardiovascular diseases (CVD) are the leading cause of global mortality and their pathogenesis lies mainly in the atherosclerotic process. There are close connections linking oxidative stress and inflammation to endothelial dysfunction, atherosclerosis and, consequently, to CVD. This review focuses on the role of xanthine oxidoreductase (XOR) and its products on the development of chronic inflammation and oxidative stress, responsible for atheromatous plaque formation. Evidence is reported that an excessive level of XOR products favors inflammatory response and plaque development, thereby promoting major cardiovascular risk factors. Also, the relationship between hyperuricemia and hypertension as well as between XOR activity and CVD is confirmed. In spite of the increasing number of clinical studies investigating the output of cardiovascular patients treated with urate-lowering therapies (including uricosuric drugs, XOR inhibitors and recombinant uricase) the results are still uncertain. The inhibition of XOR activity appears more promising than just the control of uricemia level in preventing cardiovascular events, possibly because it also reduces the intracellular accumulation of urate, as well as the production of reactive oxygen species. However, XOR inhibition also reduces the availability of the multifaced mediator nitric oxide and, at present, can be recommended only in hyperuricemic patients.