ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH GOUT AND ASYMPTOMATIC HYPERURICEMIA: AN INTEGRATIVE LITERATURE REVIEW
DOI:
https://doi.org/10.58676/sjmas.v4i3.160Keywords:
Oxidative stress, Nitric oxide, Gout, Hyperuricemia, Endothelial dysfunctionAbstract
Introduction: Endothelial dysfunction is a key pathophysiological mechanism underlying cardiovascular disease and is characterized by reduced nitric oxide bioavailability, increased oxidative stress, and enhanced inflammatory activity. Growing scientific evidence suggests a relationship between endothelial dysfunction, gout, and asymptomatic hyperuricemia. While hyperuricemia has traditionally been viewed primarily as a precursor to gout, recent research indicates that elevated uric acid levels may independently contribute to vascular impairment. This integrative review aims to analyze the existing evidence regarding the relationship between endothelial dysfunction, gout, and asymptomatic hyperuricemia and to explore the potential mechanisms linking these conditions.
Methods: An integrative literature review was conducted using PubMed, CAPES Periodicals Portal, and IntraMed databases. The search included the descriptors “endothelial dysfunction,” “endothelial function,” “hyperuricemia,” and “gout,” combined using Boolean operators. Inclusion criteria comprised full-text studies published within the last 20 years in English, Portuguese, or Spanish that directly addressed the relationship between endothelial dysfunction and hyperuricemia or gout. After screening 369 identified articles by title, abstract, and full-text review, 18 studies were selected for analysis.
Results: The reviewed literature demonstrates a consistent association between elevated uric acid levels and endothelial dysfunction. Mechanisms identified include reduced nitric oxide bioavailability due to increased reactive oxygen species production, endothelial nitric oxide synthase (eNOS) uncoupling, activation of inflammatory pathways such as HMGB1/RAGE and NF-κB, disruption of the ADMA/DDAH pathway, mitochondrial calcium overload, and increased expression of pro-inflammatory cytokines and genes. Clinical and experimental studies also suggest that xanthine oxidase activity plays a central role in oxidative stress-mediated endothelial injury. While some uric acid-lowering therapies, such as allopurinol, show improvement in endothelial function, results remain inconsistent across pharmacological interventions.
Conclusion: The current body of evidence supports a significant association between endothelial dysfunction, gout, and asymptomatic hyperuricemia, although the precise causal nature of this relationship remains unclear. Hyperuricemia appears to contribute to vascular injury through oxidative stress, inflammation, and nitric oxide pathway disruption. Given the rising global prevalence of hyperuricemia and gout, further clinical and mechanistic studies are necessary to clarify causality and guide preventive and therapeutic strategies aimed at reducing cardiovascular risk.
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