Hyperuricemia: A key contributor to endothelial dysfunction in cardiovascular diseases

Abstract

As an end product of purine metabolism, uric acid (UA) is a major endogenous antioxidant in humans. However, impaired UA synthesis and excretion can lead to hyperuricemia (HUA), which may in turn induce endothelial dysfunction (ED) and contribute to the pathogenesis of cardiovascular diseases (CVDs; e.g., atherosclerosis and hypertension). In this review, we discuss recent advances and novel insights into the effects exerted by HUA conditions in ED and related underlying mechanisms focusing on impaired UA metabolism, reduction in the synthesis and bioavailability of nitric oxide, endothelial cell injury, the endothelial‐to‐mesenchymal transition, insulin resistance, procoagulant activity, and acquisition of an inflammatory phenotype. We additionally discuss intervention strategies for HUA‐induced ED and the paradoxical roles of UA in endothelial function. We summarize major conclusions and perspectives: the deleterious effects of HUA contribute to the initiation and progression of CVD‐related ED. However, the treatment strategies (in addition to urate‐lowering therapy) for increasing endothelial function are limited because the majority of literature on pharmacological and pathophysiological mechanisms underlying HUA‐induced ED solely describes in vitro models. Therefore, a better understanding of the mechanisms involved in HUA‐induced ED is critical to the development of novel therapies for preventing and treating CVD‐HUA comorbidities.

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Perfluoroalkyl/Polyfluoroalkyl Substances: Links to Cardiovascular Disease Risk

“…There is growing recognition that hyperuricemia is a risk factor for CVD 40,41 with evidence that uric acid interferes with vascular endothelial function owing to mechanisms related to oxidative stress, inflammation, and reduced nitric oxide bioavailability. 129 Two prospective studies have investigated the association between PFAS and increased serum uric acid, with differing conclusions (Table 6;Figure). Both studies reported that PFOA was associated with increased serum uric acid.…”

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