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Expert opinion on therapeutic targets

The uric acid metabolism pathway as a therapeutic target in hyperuricemia related to metabolic syndrome.


PMID 23020656

Abstract

Uric acid (UA) increase is considered an important risk factor for the development of cardiovascular disease (CVD) favoring oxidative stress and endothelial dysfunction and is also involved in metabolic syndrome (MS) pathophysiology. Insulin has a physiological action on renal tubules, causing a reduction in UA clearance, what could explain the hyperuricemia found in MS. On the other hand, it was also hypothesized a causal role of UA in fructose-induced MS. Moreover, it has been suggested that higher UA levels predict the development of MS. MS subjects present a redox imbalance and UA participates in this process. UA can contribute to oxidative stress present in MS; however, it has also an important role in the antioxidant defense system. Although UA may have a protective effect due to its antioxidant properties, it is clear that the dominant effect of UA in MS is deleterious. All-cause mortality and CVD have been shown to be increased with higher UA levels. It is extremely important to prescribe drugs which concomitantly decrease hyperuricemia and improve co-morbidities associated with hyperuricemia. Long-term studies to verify the consequences of decreasing UA concentration below current recommendations in asymptomatic patients are needed.