Cardiovascular Disease in Gout and the Protective Effect of Treatments Including Urate-Lowering Therapy

M, Gupta; Singh, Jasvinder A.

doi:10.1007/s40265-019-01081-5

Cited by 52 publications

(41 citation statements)

References 62 publications

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“…A recent review analyzes the role of hyperuricemia and gout in hypertension and cardiovascular disease and the effect of urate-lowering therapy. Allopurinol shows cardioprotective benefits due mainly to the decrease in the serum level of uric acid and the consequent decrease in inflammation and oxidative stress [90].…”

Section: Discussionmentioning

confidence: 99%

Pro-Aging Effects of Xanthine Oxidoreductase Products

et al. 2020

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The senescence process is the result of a series of factors that start from the genetic constitution interacting with epigenetic modifications induced by endogenous and environmental causes and that lead to a progressive deterioration at the cellular and functional levels. One of the main causes of aging is oxidative stress deriving from the imbalance between the production of reactive oxygen (ROS) and nitrogen (RNS) species and their scavenging through antioxidants. Xanthine oxidoreductase (XOR) activities produce uric acid, as well as reactive oxygen and nitrogen species, which all may be relevant to such equilibrium. This review analyzes XOR activity through in vitro experiments, animal studies and clinical reports, which highlight the pro-aging effects of XOR products. However, XOR activity contributes to a regular level of ROS and RNS, which appears essential for the proper functioning of many physiological pathways. This discourages the use of therapies with XOR inhibitors, unless symptomatic hyperuricemia is present.

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Section: Discussionmentioning

confidence: 99%

Pro-Aging Effects of Xanthine Oxidoreductase Products

et al. 2020

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“…Both clinical studies and basic research evidence suggest that hyperuricemia is associated with the development and progression of cardiovascular diseases (CVDs), while the pathogenic mechanisms remain elusive ( 26 – 28 ). A recent study demonstrated that a high blood level of UA was associated with vascular inflammation ( 29 ) and endothelial dysfunction, leading to CVDs ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

miR-214 Protects Against Uric Acid-Induced Endothelial Cell Apoptosis

Yang

Zhu

et al. 2020

Front. Med.

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Background: Uric acid (UA) has been reported to be an important risk factor for cardiovascular diseases and can cause endothelial cell apoptosis through unclear mechanisms. Accumulating evidence has demonstrated that miR-214 plays a pivotal role in the pathogenesis of cardiovascular diseases. This study was to investigate the role of miR-214 in UA-induced endothelial cell apoptosis and the underlying mechanism. Material and methods: We enrolled 30 patients with hyperuricemia and 32 healthy controls and analyzed the levels of miR-214 in the serum of the participants. Then mouse aorta endothelial cells (MAECs) were treated with UA to induce cell apoptosis. An miR-214 mimic and a specific COX-2 inhibitor (NS398) were used to confirm the roles of these molecules in mediating UA-induced MAEC apoptosis or COX-2/PGE 2 cascade activation. Results: A significant reduction in circulating miR-214 in the hyperuricemia patients compared with the healthy controls, along with a negative correlation with UA levels was observed. In the MAECs, UA treatment strikingly increased apoptosis as shown by the upregulation of BAX and cleaved Caspase-3 and the increased number of apoptotic cells. Interestingly, the expression of COX-2 was also upregulated at both the protein and mRNA levels during UA-induced cell apoptosis. In addition, an miR-214 mimic blocked UA-induced MAEC apoptosis, COX-2 induction and PGE 2 secretion. The inhibition of COX-2 markedly ameliorated UA-induced apoptotic response and PGE 2 production in MAECs. Luciferase activity assays further confirmed that COX-2 is a target gene of miR-214 in endothelial cells. Conclusion: We concluded that miR-214 could alleviate UA-induced MAEC apoptosis possibly by inhibiting the COX-2/PGE 2 cascade.

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“…Higher concentrations of SUA have been shown to induce endothelial dysfunction, mediate pro-oxidative effects on vascular cells, and stimulate the production of a variety of inflammatory mediators [ 29 , 30 ]. Hyperuricemia is also known to be associated with hypertension, CKD, DM, and cardiovascular and cerebrovascular diseases [ 31 – 36 ]. However, UA has multifaceted effects on the physiology and pathology of the human body.…”

Section: Discussionmentioning

confidence: 99%