Abstract
Background: Formerly, hyperuricemia was mainly restricted to the rich population, but now-a-days it is a condition affecting wide parts of western civilization. Although only a minority of our population develops clinically relevant symptomatic hyperuricemia, there is growing evidence that elevated serum uric acid levels might be associated with elevated cardiovascular risk and cardiovascular disease progression. But it is not clear whether uric acid is just a biomarker or exerts detrimental effects itself. The xanthine oxidoreductase (XOR) is an essential enzyme for the generation of uric acid. A typical pharmacological therapy to reduce the uric acid amounts is inhibition of XOR. There is good evidence that inhibition of uric acid reduces cardiovascular events in patients. The question arises if XOR inhibition might be an attractive target to reduce cardiovascular events in patients with high or even normal uric acid levels.
Method: This review summarizes the available publications on the relationship between XOR and cardiovascular co-morbidities.
Results: The association of elevated serum uric acid level with oxidative damage in the vessel wall, inflammatory and proliferative vascular changes, hypertension and impaired kidney function are depicted. In addition, the therapeutics currently approved for the treatments of hyperuricemia are outlined and an overview regarding novel, currently researched XOR inhibitors is provided.
Conclusion: Observational and small prospective studies already have given hints for positive cardiovascular effects of XOR inhibition. However, larger prospective studies investigating cardiovascular outcomes are awaited to validate the potential beneficial effect of XOR inhibition for reduction of the cardiovascular burden.
Keywords: Cardiovascular disease, hyperuricemia, oxidative stress, renal insufficiency, uric acid, xanthine dehydrogenase, xanthine oxidase, xanthine oxidoreductase.
Current Pharmaceutical Design
Title:Xanthine Oxidase and its Role as Target in Cardiovascular Disease: Cardiovascular Protection by Enzyme Inhibition?
Volume: 23 Issue: 23
Author(s): Mirjam Schuchardt, Jaqueline Herrmann, Markus Tolle and Markus van der Giet*
Affiliation:
- Charite- Universitaetsmedizin Berlin, Campus Benjamin Franklin, Department of Nephrology, Hindenburgdamm 30, 12203 Berlin,Germany
Keywords: Cardiovascular disease, hyperuricemia, oxidative stress, renal insufficiency, uric acid, xanthine dehydrogenase, xanthine oxidase, xanthine oxidoreductase.
Abstract: Background: Formerly, hyperuricemia was mainly restricted to the rich population, but now-a-days it is a condition affecting wide parts of western civilization. Although only a minority of our population develops clinically relevant symptomatic hyperuricemia, there is growing evidence that elevated serum uric acid levels might be associated with elevated cardiovascular risk and cardiovascular disease progression. But it is not clear whether uric acid is just a biomarker or exerts detrimental effects itself. The xanthine oxidoreductase (XOR) is an essential enzyme for the generation of uric acid. A typical pharmacological therapy to reduce the uric acid amounts is inhibition of XOR. There is good evidence that inhibition of uric acid reduces cardiovascular events in patients. The question arises if XOR inhibition might be an attractive target to reduce cardiovascular events in patients with high or even normal uric acid levels.
Method: This review summarizes the available publications on the relationship between XOR and cardiovascular co-morbidities.
Results: The association of elevated serum uric acid level with oxidative damage in the vessel wall, inflammatory and proliferative vascular changes, hypertension and impaired kidney function are depicted. In addition, the therapeutics currently approved for the treatments of hyperuricemia are outlined and an overview regarding novel, currently researched XOR inhibitors is provided.
Conclusion: Observational and small prospective studies already have given hints for positive cardiovascular effects of XOR inhibition. However, larger prospective studies investigating cardiovascular outcomes are awaited to validate the potential beneficial effect of XOR inhibition for reduction of the cardiovascular burden.
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Cite this article as:
Schuchardt Mirjam , Herrmann Jaqueline , Tolle Markus and der Giet van Markus *, Xanthine Oxidase and its Role as Target in Cardiovascular Disease: Cardiovascular Protection by Enzyme Inhibition?, Current Pharmaceutical Design 2017; 23 (23) . https://dx.doi.org/10.2174/1381612823666170417130115
DOI https://dx.doi.org/10.2174/1381612823666170417130115 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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