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Abstract
Background: Gout is a common form of inflammatory arthritis that is triggered by the crystallization of monosodium urate (MSU). We investigated the potential proteins that relate to the pathogenesis or the spontaneous resolution of acute gouty arthritis.
Method: We screened for differentially expressed proteins in the plasma of patients with acute gouty arthritis using two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) identification. We confirmed these findings in a population study of 209 subjects, and further determined the protein profile of the synovial fluid (SF) from 24 gouty patients during acute attack by liquid chromatography coupled with tandem MS (LC/MS/MS).
Results: The highly expressed apolipoprotein A-I (apoA-I) was identified in the plasma of acute gouty patients compared with healthy controls. Moreover, we detected high levels of SF apoA-I in 83.3% of acute gouty patients during attack. From the population study, apoA-I was increasingly associated with normouricaemia, hyperuricaemia, and acute gouty arthritis (ptrend < 0.001), and plasma uric acid (UA) and apoA-I were positively correlated (p = 0.0156). We used a human liver cell model and found that UA enhanced the hepatic apoA-I mRNA expression level (ptrend < 0.01) and apoA-I secretion level (ptrend = 0.002) in a dose-dependent manner. An elevated MSU concentration caused the endogenous apoA-I to deplete gradually.
Conclusions: Based on the role of apoA-I in anti-inflammation, our observational data in acute gout support the hypothesis that apoA-I expression can be induced under the condition of a high concentration of UA and its elevated level may be implicated in the spontaneous resolution of acute gouty arthritis.
Acknowledgements
This study was supported by grants from the National Science Council (NSC-99-2628-B-039-009-MY3) and China Medical University Hospital (DMR-102-117 and DMR-103-093), Taiwan.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
Supplementary Table S1: Basic characteristics between healthy controls and acute gouty patients in stage I screening.
Supplementary Table S2: Primers and probes of ACTB and selected apolipoprotein genes for quantitative real-time PCR.
Supplementary Figure S1: Flowchart of whole study design.
Supplementary Figure S2: Plasma protein profiles between acute gouty patients and controls in stage I screening.
Supplementary Figure S3: The effects of UA and MSU in mRNA expression level on WRL-68 liver cell line.
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