MiR-223 alleviates thrombus and inflammation in thromboangiitis obliterans rats by regulating NLRP3

H. Zhou, C.-L. Li, P.-Z. Xia, Y.-X. He

Department of Vascular Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China. Xiaohe158@163.com

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• Angiology

OBJECTIVE: The aim of this study was to observe the regulatory effects of micro ribonucleic acid (miR)-223 on thromboangiitis obliterans (TAO) rats, and to explore the potential regulatory mechanism.

MATERIALS AND METHODS: Online database TargetScan was used to predict the downstream regulatory targets of miR-223. A total of 45 Sprague Dawley (SD) rats were randomly divided into three groups, including sham operation group (Sham group), Model group, and miR-223 agonist group (miR-223 mimic group). TAO model was successfully established in rats through the injection of lauric acid via the femoral artery. The content of serum thromboxane B2 (TXB2) and endothelin (ET) was measured via enzyme-linked immunosorbent assay (ELISA). The pathological changes in the left hind limb were detected via hematoxylin-eosin (HE) staining. Moreover, the expressions of interleukin-6 (IL-6) and IL-1β in the tissues of the rat left hind limb were determined via immunohistochemistry. In addition, the protein expression of Nod-like receptor protein 3 (NLRP3) in tissues was determined using Western blotting.

RESULTS: TargetScan database predicted that NLRP3 was the downstream target gene of miR-223. Compared with the Sham group, Model group exerted significantly higher content of serum TXB2 and ET, severe lesions in the rat left hind limb, as well as significantly increased expressions of IL-6 and IL-1β and protein expression of NLRP3 in tissues of the rat left hind limb (p<0.05). Besides, compared with the Model group, miR-223 mimic group showed remarkably lower content of serum TXB2 and ET, improved lesions in the rat left hind limb, as well as decreased expressions of IL-6 and IL-1β and protein expression of NLRP3 in the tissues of the rat left hind limb (p<0.05).

CONCLUSIONS: MiR-223 agonist can alleviate thrombus and inflammatory response in TAO rats. The possible underlying mechanism may be related to targeted regulation on NLRP3 inflammasome expression.

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