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10 November 2019 : Laboratory Research  

Elevated Uric Acid Levels Promote Vascular Smooth Muscle Cells (VSMC) Proliferation via an Nod-Like Receptor Protein 3 (NLRP3)-Inflammasome-Dependent Mechanism

Hui Li1BCDE, Fudong Qian1BEF, Heyu Liu1EF, Zhiyong Zhang2ABCDEF*

DOI: 10.12659/MSM.916667

Med Sci Monit 2019; 25:8457-8464

Abstract

BACKGROUND: Hyperuricemia has a pathogenic role in the development of hypertension and other cardiovascular diseases (CVD). Uric acid has been reported to activate Nod-like receptor protein 3 (NLRP3)-inflammasome and alter vascular smooth muscle cells (VSMC). However, the potential mechanisms underlying this association are still not understood. The aim of this study was to investigate the role and potential mechanisms of uric acid in proliferation of VSMC.

MATERIAL AND METHODS: Cell Counting Kit-8 (CCK-8) proliferation assay and colony formation assay were performed to determine the proliferative ability of VSMC under uric acid stimulation. Immunofluorescence microscopy was carried out to determine the expression of Alpha-smooth muscle actin (α-SMA). In addition, real-time PCR and Western blot were used to detect the expression of NLRP3-inflammasome, and ELISA was performed to measure the levels of IL-18 and IL-1β.

RESULTS: The results showed that uric acid increases the proliferation of VSMC and induces α-SMA accumulation. We also found that uric acid increases the level of NLRP3 and induces NLRP3-inflammasome activation. The expressions of uric acid-induced inflammatory markers IL-1β and IL-18 were decreased by the inhibitor MCC950.

CONCLUSIONS: Our findings revealed that uric acid induces inflammation through NLRP3-inflammasome-mediated VSMC proliferation. NLRP3 may be a new therapeutic target for hypertension.

Keywords: hyperuricemia, Muscle, Smooth, Vascular, Nod Signaling Adaptor Proteins, Uric Acid, Actins, Cardiovascular Diseases, Carrier Proteins, Cell Line, Hypertension, Inflammasomes, Interleukin-18, Myocytes, Smooth Muscle, NLR Family, Pyrin Domain-Containing 3 Protein

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750