LncRNA-5829: a novel inhibitor of cardiac fibrosis.

Background: Recent studies have proved that long non-coding RNAs (lncRNAs) are closely related to the pathogenesis of cardiovascular diseases (CVDs), but their exact regulatory mechanism including non-coding as well as coding function in myocardial fibrosis need to be further explored. This study aims to explore the role of a novel and highly conserved lncRNA-5829 in myocardial fibrosis.

Methods: Thirty-two male C57BL/6 mice weighing 20-25 g (8 weeks old) were cultured under specific pathogen-free (SPF) conditions prior to the start of the experiment. Myocardial fibrosis cells and mouse models were established by transforming growth factor-β1 (TGF-β1) induction and ligation of the left anterior descending coronary artery (LAD) surgery. After cell overexpression or knockdown of lncRNA-5829, the levels of myocardial fibrosis markers, cell proliferation, cell viability, and α smooth muscle actin (α-SMA) were measured by real-time polymerase chain reaction (PCR), Western blot and 5-ethynyl-2'-deoxyuridine (EdU) staining, cell counting kit-8 (CCK-8), immunofluorescence technique, respectively. After mouse tail vein injection of lncRNA-5829 overexpression plasmid, the levels of myocardial fibrosis markers, cardiac function, myocardial collagen distribution, and myocardial injury were measured by real-time PCR, Western blot, and echocardiography, Masson staining, and hematoxylin-eosin staining (HE staining), respectively. Furthermore, the localization of lncRNA-5829 in cardiac fibroblasts was observed by the fluorescent in situ hybridization (FISH) assay.

Results: The expression of lncRNA-5829 is downregulated in myocardial fibrosis. In vivo models, following myocardial infarction (MI) induction, the expression of lncRNA-5829 significantly decreased compared to the sham group (P<0.001); in vitro models, after TGF-β1 induction, the expression of lncRNA-5829 also significantly decreased compared to the control group (P<0.001). Knockdown of lncRNA-5829 promoted the expression of fibronectin 1 (FN1) (P=0.002), collagen type I alpha 1 (Col1α1) (P=0.004), and collagen type III alpha 1 (Col3α1) (P=0.001) at the mRNA level, and FN1 (P=0.004), Col1α1 (P<0.001) at the protein level induced by TGF-β1. In contrast, overexpression of lncRNA-5829 could downregulate the expression of factors related to myocardial fibrosis, thereby inhibiting the progression of myocardial fibrosis. Overexpression of lncRNA-5829 in vivo significantly inhibited collagen deposition in the myocardial tissue of mice with MI (P=0.01) and improved cardiac function.

Conclusions: This study demonstrated that lncRNA-5829, as a new anti-fibrotic factor, may play an important role in regulating the pathological process of myocardial fibrosis, and is a potential molecular target for the treatment of cardiac fibrosis and related heart diseases.