Journal of Nursing

The Key Role of Hyperuricemia in Oxidative Stress, Inflammatory Response, and Endothelial Dysfunction

Huan Yi, Fachun Zhou, Shijing Tian, Sanle Jiang


Uric acid is the end product of purine metabolism in humans. A growing body of experimental and clinical evidence suggests that hyperuricemia has pathogenic effects in vivo such as inducing oxidative stress, promoting inflammatory responses, and causing endothelial dysfunction, and is involved in affecting systemic inflammatory responses and hemodynamics by a variety of mechanisms. This review will provide an overview of the role of hyperuricemia in oxidative stress, inflammatory response, and endothelial dysfunction.


Hyperuricemia; Oxidative Stress; Inflammation; Endothelial Dysfunction

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Chinese Medical Association, Chinese Medical Journals Publishing House, Chinese Society of General Practice, Chinese Association of Gout Study, et al.Guideline for primary care of gout and hyperuricemia(2019) [J] Chinese Journal of General Practitioners, 2020, 19(4): 293-303.

Alvarez-Lario B, Maccaron-Vicente J: Is there anything good in uric acid? QJ Med 2011; 104: 1015–1024.

Nakagawa T, Kang DH, Feig D, et al. Un- earthing uric acid: an ancient factor with re-cently found significance in renal and cardio- vascular disease [J]. Kidney Int, 2006, 69 (10): 1722-1725.

Johnson RJ, Kang DH, Feig D, et al. Is there a pathogenetic role for uric acid in hyper- tension and cardiovascular and renal disease? [J]. Hypertension, 2003, 41 (6): 1183-1190.

Wang H., Zhang H., Sun L., Guo W. Roles of hyperuricemia in metabolic syndrome and cardiac-kidney-vascular system diseases. American Journal of Translational Research. 2018, 10(9): 2749–2763.

Komori H., Yamada K., Tamai I. Hyperuricemia enhances intracellular urate accumulation via down-regulation of cell-surface BCRP/ABCG2 expression in vascular endothelial cells. Biochimica et Biophysica Acta (BBA) - Biomembranes. 2018;1860(5):973–980.

Ngo JS., Ho MHM. Evaluation of rasburicase use in the Fraser Health Authority: a retrospective review. The Canadian Journal of Hospital Pharmacy. 2019; 72(4): 311–319.

Zhou X, Matavelli L, Frohlich ED, Uric acid: its relationship to renal hemodynamics and the renal renin-angiotensin system. Curr Hypert Rep 2006; 8: 120-124.

Yu MA, Sanchez-Lozada LG, Johnson RJ, Kang DH. Oxidative stress with an activation of the renin-angiotensin system in human vascular endothelial cells as a novel mechanism of uric acid-induced endothelial dysfunction. Journal of Hypertension. 2010;28(6):1234-1242.

Roumeliotis S., Roumeliotis A., Dounousi E., Eleftheriadis T., Liakopoulos V. Dietary antioxidant supplements and uric acid in chronic kidney disease: a review. Nutrients. 2019;11(8):p. 1911.

Doehner W., Schoene N., Rauchhaus M., et al. Effects of xanthine oxidase inhibition with allopurinol on endothelial function and peripheral blood flow in hyperuricemic patients with chronic heart failure: results from 2 placebo-controlled studies. Circulation. 2002; 105(22): 2619–2624.

Yang L., Chang B., Guo Y., Wu X., Liu L. The role of oxidative stress-mediated apoptosis in the pathogenesis of uric acid nephropathy. Renal Failure. 2019; 41(1): 616-622.

Sánchez-Lozada LG., Lanaspa MA., Cristóbal-García M., et al. Uric acid- induced endothelial dysfunction is associated with mitochondrial alterations and decreased intracellular ATP concentrations. Nephron Experimental Nephrology. 2013; 121(3-4): e71-e78.

Kadowaki D., Sakaguchi S., Miyamoto Y., et al. Direct radical scavenging activity of benzbromarone provides beneficial antioxidant properties for hyperuricemia treatment. Biological & Pharmaceutical Bulletin. 2015; 38(3): 487– 492.

Lu WJ et al. “Uric Acid Produces an Inflammatory Response through Activation of NF-κB in the Hypothalamus: Implications for the Pathogenesis of Metabolic Disorders.” Scientific reports vol. 5 12144. 16 Jul. 2015.

Kim S. M., Lee S. H., Kim Y. G., et al. Hyperuricemia-induced NLRP3 activation of macrophages contributes to the progression of diabetic nephropathy. American Journal of Physiology-Renal Physiology. 2015;308(9):F993–F1003.

Rabadi MM., Kuo MC., Ghaly T., et al. Interaction between uric acid and HMGB1 translocation and release from endothelial cells. American Journal of Physiology-Renal Physiology. 2012;302(6): F730–F741.

Choe JY., Choi CH., Park KY., Kim SK. High-mobility group box 1 is responsible for mono- sodium urate crystal-induced inflammation in human U937 macrophages. Biochemical and Biophysical Research Communications. 2018; 503(4): 3248-3255.

Iribarren C, Folsom AR, Eckfeldt JH, McGovern PG, Nieto FJ. Correlates of uric acid and its association with asymptomatic carotid atherosclerosis: the ARIC Study.

WANG Y,BAO X. Effects of uric acid on endothelial dysfunction in early chronic kidney dis ease and its mechanisms [J]. Eur J Med Res,2013,18:26.

Li P., Zhang L., Zhang M., Zhou C., Lin N. Uric acid enhances PKC-dependent eNOS phosphorylation and mediates cellular ER stress: a mechanism for uric acid-induced endothelial dysfunction.

International Journal of Molecular Medicine. 2016; 37(4): 989–997.

Kanellis J, Watanabe S, Li JH, Kang DH, Li P, Nakagawa T, Wamsley A, Sheikh-Hamad D, Lan HY, Feng L, Johnson RJ. Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase-2. Hypertension. 2003 Jun; 41(6):1287-93.

Long CL., Qin XC., Pan ZY., et al. Activation of ATP-sensitive potassium channels protects vascular endothelial cells from hypertension and renal injury induced by hyperuricemia. Journal of Hypertension. 2008; 26(12):2326-2338.



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