Inflammation, oxidative stress and lipids: the risk triad for atherosclerosis in gout.
For many years, the relationship between cardiovascular disease risk and gout, though strong and consistent, was suspected of being coincidental rather than causative. In recent years, compelling epidemiological and clinical data have increasingly favoured an aetiological connection. However, that connection is notably complex, involving a multifaceted model that includes interactions between inflammatory processes, oxidative stress and potential genetic influences, as well as cardiovascular and renal components that remain only partly explained. Urate appears to be able to activate the immune response, and in that context has a mediating role in the inflammatory process via the inflammasome. This interaction of urate and inflammation is central to the inflammatory cascade associated with gout flares. In the arena of oxidative stress, urate has both antioxidant and pro-oxidant properties, and while potentially beneficial in scavenging free radicals, it can also impair endothelial function and thereby give rise to atherosclerotic risk. Human and animal studies have revealed associations between hyperuricaemia and a host of atherosclerotic risk factors, whereas a reduction in urate levels is frequently associated with improvement or even resolution of such risk factors. The degree to which reduction of serum urate can reliably improve cardiovascular risk remains uncertain. It is hoped that the introduction of newer urate-lowering agents may help to clarify this picture and improve treatment options for both gout and atherosclerosis.
Krishnan
Eswar
E
Division of Immunology and Rheumatology, Stanford University School of Medicine, Palo Alto, CA, USA. e.krishnan@stanford.edu
D050197:Atherosclerosis / Q000209:etiology*; D006073:Gout / Q000150:complications*; D006801:Humans; D033461:Hyperuricemia / Q000150:complications*; D058847:Inflammasomes / Q000097:blood / Q000378:metabolism*; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D012306:Risk; D014527:Uric Acid / Q000097:blood / Q000378:metabolism*
D058847:Inflammasomes; D008055:Lipids; D014527:Uric Acid