Expression profile of lncRNAs of aortic remodeling in a murine aortic arch constriction model / 解放军医学杂志

ABSTRACT

Objective To study the expression profile and possible mechanism of long non-coding RNA (lncRNA) of aortic remodeling induced by elevated blood pressure in a murine transverse aortic arch constriction (TAC) model. Methods Sixty 8-week-old male C57BL/6J mice were randomly and averagely divided to receive TAC surgery or sham operation. TAC model mice were included in the experimental group when the ratio of blood flow velocity of right common carotid artery/left common carotid artery (RC/LC) was 5-10 at 1 week after operation, and mice treated with sham operation were included in the control group when RC/LC was less than 1. Twenty four mice for each group met the criteria in the end. HE staining, Weigert staining and Sirius red staining were used to observe the media wall thickness, elastic fiber and collagen fiber deposition of the ascending aorta. Two weeks after the surgery, aortic tissues were harvested for high throughput sequencing to identify differentially expressed lncRNA. Bioinformatics analysis were then performed to analyze the changes of lncRNA expression. Results One week after modeling, the ultrasound results showed that the blood flow velocity increased significantly at the ascending aorta in experimental group, and the blood flow velocity ratio (RC/LC) was higher significantly in experimental group than in control group (P<0.001). Two weeks after modeling and compared to that in control group, the inner diameter of the ascending aorta enlarged in experimental group and the tunica media of ascending aorta developed obvious remodeling, including the thickening of the tunica media, the thinning of media elastic fibers and the deposition of a large amount of collagen fibers. Using the well established cutoffs (fold change ≥2, P<0.05 and false discovery rate (FDR) <0.05), a total of 199 lncRNAs were significantly changed in experimental group and control group at transcription level. Six differentially expressed lncRNAs were randomly selected for verifying the accuracy of sequencing data by using qRT-PCR, which was consistent with the sequencing results. Target genes of differentially expressed lncRNAs were predicted by antisense and/or cis-regulatory module prediction. Predicted target genes were further analyzed by Gene Ontology (GO) and Kyoto Enrichment of Genes and Genomes pathway analysis (KEGG) to find the enriched cellular component, molecular function, biological process, and signaling pathways. The results showed that target genes related to extracellular matrix, cell matrix adhesion, NF-κB pathway and vascular smooth muscle cell contraction were significantly enriched. Conclusions An overview of lncRNA expression changes in aortic remodeling induced by high pressure overload has been provided in present paper. It indicates that lncRNA is involved in the extracellular matrix synthesis process that regulates the arterial remodeling, and may help to clarify the potential molecule mechanism of aortic remodeling caused by elevated blood pressure.