Session Title: Metabolic and Crystal Arthropathies: Mechanisms of Disease
Session Type: Abstract Submissions (ACR)
Excess amount of uric acid in human body causes acute inflammation, gout. In addition, uric acid is identified as a danger signal and is implicated in playing roles in chronic inflammatory processes. Recently several retrospective studies have reported that serum uric acid might be one of the independent risk factors of atherosclerosis. However there has been no prospective study showing the association of serum uric acid level and atherosclerosis. It’s not still clear whether uric acid progresses atherosclerosis. Using the transgenic mice expressed uricase, anuric acid hydrolytic enzyme, we investigated the reduction of serum uric acid level could prevent atherosclerosis in mice.
We prepared uricase transgenic mice based in C57BL/6 mice. They expressed the urcase secreted to extracellular space and their serum uric acid level were decreased. We bred UricaseTg mice with LDL receptor deficient or apolipoprotein E deficient mice to develop LDLR-/-UricaseTg mice or ApoE-/-UricaseTg mice, respectively. LDLR-/-UricaseTg mice, ApoE-/-UricaseTg mice and control mice (LDLR-/- mice and ApoE-/-mice) at 6 weeks of age received high-fat diet for 16 weeks. Then their hearts and aortas were removed at 22 weeks of age. Aortic sinuses of these mice were fixed and sliced into 8 micrometer. We measured atherosclerosis area of each slice and computed volume of lesions of aortic sinus. Aortas of these mice were stained with oil red O and measured area of atherosclerosis lesions. We calculated ratio of the lesion area to whole aortic area.
The volumes of atherosclerosis lesions in aortic sinuses of LDLR-/-UricaseTg (0.158±0.016 mm3) [n=17] were smaller than that of LDLR-/- (0.231±0.017 mm3) [n=12] [p=0.0049]. There were no significant differences between ApoE-/-UricaseTg (0.227±0.022 mm3) [n=15] and ApoE-/- (0.292±0.032 mm3) [n=7] [p=0.11]. The ratio of area of atherosclerosis in aorta was 7.4±1.2 % in LDLR-/-UricaseTg [n=14], 8.1±0.9% in LDLR-/- [n=24], 6.0±0.8% in ApoE-/-UricaseTg [n=15] and 5.3±0.6% in ApoE-/- [n=7]. There were little differences between each group (LDLR-/-UricaseTg vs LDLR-/-UricaseTg [p=0.63], ApoE-/-UricaseTg vs ApoE-/-[p=0.63]).
Although there was a discrepancy between atherosclerosis prone strains, the results showed that the reduction of serum uric acid level by expressing secretable uriasemay inhibit the progression of atherosclerosis.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-reduction-of-serum-uric-acid-level-might-prevent-atherosclerosis-in-mice/