LncRNA ROR facilitates myocardial fibrosis in rats with viral myocarditis through regulating C-Myc expression

N. Zhang, Y. Sun

Department of Internal Medicine-Cardiovascular, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, China. sunyao2121@163.com

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• Cardiology

OBJECTIVE: The aim of this study was to explore the effect of long non-coding ribonucleic acid (lncRNA) ROR on myocardial fibrosis in rats with viral myocarditis by regulating c-myc expression.

MATERIALS AND METHODS: A total of 120 healthy male rats were randomly divided into three groups, including: blank control group (group N, healthy rats, n=40), model control group (group M, viral myocarditis, n=40), and group P (lncRNA ROR + viral myocarditis, n=40). At 5, 10, and 15 d after modeling, the rats were sacrificed. Meanwhile, the left ventricular mass index (LVMI), the left ventricular weight/tibial length (LVW/TL) and the heart mass index (HMI) were measured, respectively. The myocardial tissues of rats were observed via staining. The protein and mRNA expressions of the transforming growth factor-β (TGF-β) and c-myc in myocardial tissues were detected via Western blotting and quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), respectively. Moreover, the level of the serum interleukin-6 (IL-6) was detected via enzyme-linked immunosorbent assay (ELISA).

RESULTS: Compared with group N, HMI, LVMI, and LVW/TL in group M significantly increased at each time point (p<0.01). Meanwhile, they were remarkably elevated at each time point in group P when compared with those in group M (p<0.01). According to the results of hematoxylin-eosin staining (HE) staining, the myocardial fibers were normal and orderly arranged in group N. Meanwhile, no inflammatory cells were observed in group N. In group M, the proliferation of a large number of inflammatory cells was observed, and the myocardial cells were disorderly arranged and became enlarged. In group P, the myocardial fibrosis was significantly severer than that of the other two groups (p<0.05). The results of the Masson staining revealed that there was significantly less accumulation of collagen fibers in myocardium in group N. There was a little accumulation of collagen fibers in the myocardium and fibrosis declined in group M. The myocardial fibrosis in group P remarkably increased when compared with group M (p<0.05). According to the results of the Western blotting, the protein expressions of c-myc and TGF-β were significantly up-regulated in group P, compared with those in group M and N (p<0.05). However, they were remarkably higher in group M than in group N (p<0.05). QRT-PCR showed that the relative messenger ribonucleic acid (mRNA) expressions of c-myc and TGF-β were remarkably up-regulated in group P when compared with those in group M and N, showing statistically significant differences (p<0.05). Moreover, they were significantly higher in group M than those in group N (p<0.05). Besides, the expression level of serum IL-6 remained highest in group P (p<0.01).

CONCLUSIONS: LncRNA ROR up-regulates the expression of c-myc and increases the level of serum IL-6, thereby facilitating the proliferation and differentiation of cardiac fibroblasts.

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