Uric Acid in Inflammation and the Pathogenesis of Atherosclerosis

Kimura, Yoshitaka; Tsukui, Daisuke; Kono, Hajime

doi:10.3390/ijms222212394

Cited by 152 publications

(136 citation statements)

References 120 publications

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“…XO will be converted in UA and superoxide anion, which will lead to high intracellular amounts of superoxide anions, which may induce cell envelope damage and enhanced mutagenesis. Only mammals have XO type [ 22 ]. XDH is the most common form of XOR and, by the conversion through UA, will develop a reduced form of nicotinamide adenine nucleotide (NADH).…”

Section: Uric Acid Synthesismentioning

confidence: 99%

“…In conditions that cause exposure to a hypoxic environment, such as advanced cardiac failure, pulmonary disorders, sepsis, intoxications, and others, XDH will be converted into XO [ 23 ] ( Figure 1 ). XO has an important role in preventing infections by producing mitochondrial ROS although excess formation will imbalance the oxidative and anti-oxidative equilibrium and subsequently promote a pro-inflammatory status [ 22 ]. Furthermore, once UA is synthetized, it will be transported to the circulatory system and excreted through renal and gastrointestinal pathways [ 24 ].…”

Section: Uric Acid Synthesismentioning

confidence: 99%

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Uric Acid and Oxidative Stress—Relationship with Cardiovascular, Metabolic, and Renal Impairment

Gherghina

Peride

Ţigliş

et al. 2022

IJMS

136

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Background: The connection between uric acid (UA) and renal impairment is well known due to the urate capacity to precipitate within the tubules or extra-renal system. Emerging studies allege a new hypothesis concerning UA and renal impairment involving a pro-inflammatory status, endothelial dysfunction, and excessive activation of renin–angiotensin–aldosterone system (RAAS). Additionally, hyperuricemia associated with oxidative stress is incriminated in DNA damage, oxidations, inflammatory cytokine production, and even cell apoptosis. There is also increasing evidence regarding the association of hyperuricemia with chronic kidney disease (CKD), cardiovascular disease, and metabolic syndrome or diabetes mellitus. Conclusions: Important aspects need to be clarified regarding hyperuricemia predisposition to oxidative stress and its effects in order to initiate the proper treatment to determine the optimal maintenance of UA level, improving patients’ long-term prognosis and their quality of life.

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Section: Uric Acid Synthesismentioning

confidence: 99%

Section: Uric Acid Synthesismentioning

confidence: 99%

Uric Acid and Oxidative Stress—Relationship with Cardiovascular, Metabolic, and Renal Impairment

Gherghina

Peride

Ţigliş

et al. 2022

IJMS

136

View full text Add to dashboard Cite

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“…Uric acid has been associated with CV diseases and with inflammation and oxidative stress. In addition, the majority of these studies showed that elevated levels of uric acid are a potential contributor risk factor in the development and progression of CKD [ 186 , 187 ].…”

Section: Improvement Of Conventional CV and Renal Risk Factors By Sgl...mentioning

confidence: 99%

An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors

Salvatore

Galiero

Caturano

et al. 2022

IJMS

114

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Sodium-glucose co-transporter 2 (SGLT2) inhibitors block glucose reabsorption in the renal proximal tubule, an insulin-independent mechanism that plays a critical role in glycemic regulation in diabetes. In addition to their glucose-lowering effects, SGLT2 inhibitors prevent both renal damage and the onset of chronic kidney disease and cardiovascular events, in particular heart failure with both reduced and preserved ejection fraction. These unexpected benefits prompted changes in treatment guidelines and scientific interest in the underlying mechanisms. Aside from the target effects of SGLT2 inhibition, a wide spectrum of beneficial actions is described for the kidney and the heart, even though the cardiac tissue does not express SGLT2 channels. Correction of cardiorenal risk factors, metabolic adjustments ameliorating myocardial substrate utilization, and optimization of ventricular loading conditions through effects on diuresis, natriuresis, and vascular function appear to be the main underlying mechanisms for the observed cardiorenal protection. Additional clinical advantages associated with using SGLT2 inhibitors are antifibrotic effects due to correction of inflammation and oxidative stress, modulation of mitochondrial function, and autophagy. Much research is required to understand the numerous and complex pathways involved in SGLT2 inhibition. This review summarizes the current known mechanisms of SGLT2-mediated cardiorenal protection.

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“…Intracellular urate also generates ROS and activates inflammasomes and several proinflammatory signalling pathways, resulting in proatherogenic responses. 42 Therefore, it would be theoretically reasonable that chronic inflammation and atherosclerosis progression are attenuated by SU-lowering via pharmacological XO inhibition. However, the levels of hs-CRP, a representative marker indicative of inflammatory status, were unchanged by febuxostat treatment, even at high doses, despite a substantial decrease in the SU concentration.…”

Section: Discussionmentioning

confidence: 99%

Association between serum urate level and carotid atherosclerosis: an insight from a post hoc analysis of the PRIZE randomised clinical trial

et al. 2022

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ObjectivesElevated serum urate (SU) levels are associated with arterial atherosclerosis and subsequent cardiovascular events. However, an optimal therapeutic target SU level for delaying atherosclerotic progression in patients with hyperuricaemia remains uncertain. The aim of this analysis was to assess an association between changes in SU level and carotid intima–media thickness (IMT) to examine whether an optimal SU concentration exists to delay atherosclerotic progression.MethodsThis was a post hoc analysis of the PRIZE (programme of vascular evaluation under uric acid control by xanthine oxidase inhibitor, febuxostat: multicentre, randomised controlled) study of Japanese adults with asymptomatic hyperuricaemia. The primary endpoint of this analysis was an association between changes in SU levels and mean common carotid artery IMT (CCA-IMT) after 24 months of febuxostat treatment.ResultsAmong subjects treated with febuxostat (n=239), a total of 204 who had both data on SU and mean CCA-IMT at baseline and 24 months were included in this analysis. The mean baseline SU level was 7.7±1.0 mg/dL, and febuxostat treatment significantly reduced SU concentrations at 24 months (estimated mean change ‒3.051 mg/dL, 95% CI ‒3.221 to ‒2.882). A multivariable linear regression analysis revealed that a reduction in SU level was associated with changes in mean CCA-IMT values at 24 months (p=0.025). In contrast, the achieved SU concentrations were not associated with changes in mean CCA-IMT at 24 months.ConclusionA greater reduction in SU, but not its achieved concentrations, may be associated with delayed progression of carotid IMT in patients with asymptomatic hyperuricaemia treated with febuxostat.Trial registration numberUMIN000012911

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Uric Acid in Inflammation and the Pathogenesis of Atherosclerosis

Cited by 152 publications

References 120 publications

Uric Acid and Oxidative Stress—Relationship with Cardiovascular, Metabolic, and Renal Impairment

Uric Acid and Oxidative Stress—Relationship with Cardiovascular, Metabolic, and Renal Impairment

An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors

Association between serum urate level and carotid atherosclerosis: an insight from a post hoc analysis of the PRIZE randomised clinical trial

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