Abstract
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/PGE2 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 PGE2 secretion. The inhibition of COX-2 markedly ameliorated UA-induced apoptotic response and PGE2 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/PGE2 cascade.
Highlights
Uric acid (UA) is the final product of purine metabolism
To rule out the impact of BUN and TG, the correlation coefficient between miR214 and UA were determined by partial correlation analysis with BUN and TG adjustment, and multiple variable linear regression models after adjusting BUN and TG were used to further explore the associations between serum UA and miR-214 level, with the results presented as regression coefficients and 95% confidence intervals (CIs)
To determine the expression of miR-214 in hyperuricemia patients, we measured the level of miR-214 in the sera of hyperuricemia patients and sex- and age-matched healthy miR-214 in UA-Induced Endothelial Cell Apoptosis controls
Summary
Uric acid (UA) is the final product of purine metabolism. Hyperuricemia is the main cause of gout. UA miR-214 in UA-Induced Endothelial Cell Apoptosis was found to cause vascular endothelial cell apoptosis in vivo [4]. Hyperuricemia is considered to be an independent risk factor for the development of hypertension and atherosclerosis [5,6,7,8], which triggered our interest to investigate the pathogenic mechanism of UA-induced endothelial cell injury. 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
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