Uric Acid in Inflammation and the Pathogenesis of Atherosclerosis

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Nov 27

PMID 34830282

Citations 83

Authors

Yoshitaka Kimura

Daisuke Tsukui

Hajime Kono

Affiliations

Soon will be listed here.

Abstract

Hyperuricemia is a common metabolic syndrome. Elevated uric acid levels are risk factors for gout, hypertension, and chronic kidney diseases. Furthermore, various epidemiological studies have also demonstrated an association between cardiovascular risks and hyperuricemia. In hyperuricemia, reactive oxygen species (ROS) are produced simultaneously with the formation of uric acid by xanthine oxidases. Intracellular uric acid has also been reported to promote the production of ROS. The ROS and the intracellular uric acid itself regulate several intracellular signaling pathways, and alterations in these pathways may result in the development of atherosclerotic lesions. In this review, we describe the effect of uric acid on various molecular signals and the potential mechanisms of atherosclerosis development in hyperuricemia. Furthermore, we discuss the efficacy of treatments for hyperuricemia to protect against the development of atherosclerosis.

Citing Articles

Sodium-Glucose Transporter-2 Inhibitors (SGLT2i) and Myocardial Ischemia: Another Compelling Reason to Consider These Agents Regardless of Diabetes.

Piccirillo F, Lanciotti M, Nusca A, Frau L, Spano A, Liporace P Int J Mol Sci. 2025; 26(5).

PMID: 40076724 PMC: 11899902. DOI: 10.3390/ijms26052103.

Graphene-Multiwalled Carbon Nanotubes Modified Glassy Carbon Electrodes for Simultaneous Detection of Ascorbic Acid, Dopamine, and Uric Acid.

Hsieh H, Xu J, Lin J, Chiang Y, Weng Y ACS Omega. 2025; 10(8):8160-8171.

PMID: 40060814 PMC: 11886922. DOI: 10.1021/acsomega.4c09646.

Association Between Uric Acid to High-Density Lipoprotein Cholesterol Ratio and Abdominal Aortic Aneurysm: A Single-Center Retrospective Study.

Lu D, Si K, Huo G J Inflamm Res. 2025; 18:3217-3226.

PMID: 40059943 PMC: 11890351. DOI: 10.2147/JIR.S508355.

The new definition of metabolic syndrome including hyperuricemia improves its prognostic value: results from NHANES database.

Zhang Z, Pang Y, Shen J, Chen W, Hao C, Lei Z BMC Cardiovasc Disord. 2025; 25(1):93.

PMID: 39934698 PMC: 11817069. DOI: 10.1186/s12872-025-04529-7.

The Agatston score is a predictor of contrast-induced nephropathy in patients with stable coronary artery disease after percutaneous coronary intervention.

Sivri F, Icen Y, Aksoy F, Koca H, Koc M Postepy Kardiol Interwencyjnej. 2025; 20(4):406-412.

PMID: 39897010 PMC: 11783255. DOI: 10.5114/aic.2024.144774.

References

Sautin Y, Nakagawa T, Zharikov S, Johnson R . Adverse effects of the classic antioxidant uric acid in adipocytes: NADPH oxidase-mediated oxidative/nitrosative stress. Am J Physiol Cell Physiol. 2007; 293(2):C584-96. DOI: 10.1152/ajpcell.00600.2006. View

Larsen K, Pottegard A, Lindegaard H, Hallas J . Effect of Allopurinol on Cardiovascular Outcomes in Hyperuricemic Patients: A Cohort Study. Am J Med. 2015; 129(3):299-306.e2. DOI: 10.1016/j.amjmed.2015.11.003. View

Tanaka A, Taguchi I, Teragawa H, Ishizaka N, Kanzaki Y, Tomiyama H . Febuxostat does not delay progression of carotid atherosclerosis in patients with asymptomatic hyperuricemia: A randomized, controlled trial. PLoS Med. 2020; 17(4):e1003095. PMC: 7176100. DOI: 10.1371/journal.pmed.1003095. View

Ceriello A, Motz E . Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol. 2004; 24(5):816-23. DOI: 10.1161/01.ATV.0000122852.22604.78. View

Grimaldi-Bensouda L, Alperovitch A, Aubrun E, Danchin N, Rossignol M, Abenhaim L . Impact of allopurinol on risk of myocardial infarction. Ann Rheum Dis. 2014; 74(5):836-42. DOI: 10.1136/annrheumdis-2012-202972. View

Braga T, Forni M, Correa-Costa M, Ramos R, Barbuto J, Branco P . Soluble Uric Acid Activates the NLRP3 Inflammasome. Sci Rep. 2017; 7:39884. PMC: 5233987. DOI: 10.1038/srep39884. View

Vasamsetti S, Karnewar S, Kanugula A, Thatipalli A, Kumar J, Kotamraju S . Metformin inhibits monocyte-to-macrophage differentiation via AMPK-mediated inhibition of STAT3 activation: potential role in atherosclerosis. Diabetes. 2015; 64(6):2028-41. DOI: 10.2337/db14-1225. View

Rabadi M, Kuo M, Ghaly T, Rabadi S, Weber M, Goligorsky M . Interaction between uric acid and HMGB1 translocation and release from endothelial cells. Am J Physiol Renal Physiol. 2011; 302(6):F730-41. PMC: 3311321. DOI: 10.1152/ajprenal.00520.2011. View

Mackenzie I, Ford I, Nuki G, Hallas J, Hawkey C, Webster J . Long-term cardiovascular safety of febuxostat compared with allopurinol in patients with gout (FAST): a multicentre, prospective, randomised, open-label, non-inferiority trial. Lancet. 2020; 396(10264):1745-1757. DOI: 10.1016/S0140-6736(20)32234-0. View

10.

Oshima Y . [Gout]. Naika. 1966; 17(2):341-2. View

11.

Choi H, Ford E, Li C, Curhan G . Prevalence of the metabolic syndrome in patients with gout: the Third National Health and Nutrition Examination Survey. Arthritis Rheum. 2007; 57(1):109-15. DOI: 10.1002/art.22466. View

12.

Kushiyama A, Okubo H, Sakoda H, Kikuchi T, Fujishiro M, Sato H . Xanthine oxidoreductase is involved in macrophage foam cell formation and atherosclerosis development. Arterioscler Thromb Vasc Biol. 2011; 32(2):291-8. DOI: 10.1161/ATVBAHA.111.234559. View

13.

Alem M . Allopurinol and endothelial function: A systematic review with meta-analysis of randomized controlled trials. Cardiovasc Ther. 2018; 36(4):e12432. PMC: 6175067. DOI: 10.1111/1755-5922.12432. View

14.

Butler R, Morris A, Belch J, Hill A, Struthers A . Allopurinol normalizes endothelial dysfunction in type 2 diabetics with mild hypertension. Hypertension. 2000; 35(3):746-51. DOI: 10.1161/01.hyp.35.3.746. View

15.

Krishnan E, Pandya B, Chung L, Dabbous O . Hyperuricemia and the risk for subclinical coronary atherosclerosis--data from a prospective observational cohort study. Arthritis Res Ther. 2011; 13(2):R66. PMC: 3132061. DOI: 10.1186/ar3322. View

16.

Garcia-Arroyo F, Monroy-Sanchez F, Munoz-Jimenez I, Gonzaga G, Andres-Hernando A, Zazueta C . Allopurinol Prevents the Lipogenic Response Induced by an Acute Oral Fructose Challenge in Short-Term Fructose Fed Rats. Biomolecules. 2019; 9(10). PMC: 6843394. DOI: 10.3390/biom9100601. View

17.

Guthikonda S, Sinkey C, Barenz T, Haynes W . Xanthine oxidase inhibition reverses endothelial dysfunction in heavy smokers. Circulation. 2003; 107(3):416-21. DOI: 10.1161/01.cir.0000046448.26751.58. View

18.

Verzola D, Ratto E, Villaggio B, Parodi E, Pontremoli R, Garibotto G . Uric acid promotes apoptosis in human proximal tubule cells by oxidative stress and the activation of NADPH oxidase NOX 4. PLoS One. 2014; 9(12):e115210. PMC: 4267812. DOI: 10.1371/journal.pone.0115210. View

19.

Nakata T, Ikeda S, Koga S, Yonekura T, Tsuneto A, Doi Y . Randomized, Open-Label, Cross-Over Comparison of the Effects of Benzbromarone and Febuxostat on Endothelial Function in Patients with Hyperuricemia. Int Heart J. 2020; 61(5):984-992. DOI: 10.1536/ihj.20-114. View

20.

Chen-Xu M, Yokose C, Rai S, Pillinger M, Choi H . Contemporary Prevalence of Gout and Hyperuricemia in the United States and Decadal Trends: The National Health and Nutrition Examination Survey, 2007-2016. Arthritis Rheumatol. 2019; 71(6):991-999. PMC: 6536335. DOI: 10.1002/art.40807. View