心肌重构是衰老心脏的重要特征，但衰老性心肌重构的机制不明。越来越多的证据显示非编码RNA(ncRNA)参与衰老性心肌重构的病理过程。我们证实环形RNA circRNA_000203（circRNA-203）在D-半乳糖诱导衰老小鼠心肌中表达上调，过表达circRNA-203能显著增强小鼠心肌细胞和心肌成纤维细胞的肥大表型和纤维化表型。双荧光素酶报告实验和RNA pull-down结果证实circRNA-203与微小RNA miR-26b有特异结合作用。推测circRNA-203通过特异结合miR-26b来解除其对靶基因Col1a2、CTGF、MEF2C、CCND1，-2，CCNE1和CDK6的抑制作用，进而促发心肌重构。拟建立circRNA-203转基因小鼠，从整体-细胞-分子水平，阐明circRNA-203作用的分子机制，为开辟以环形RNA为靶点的衰老性心肌重构治疗研究提供科学依据。

Cardiac remodeling is an important character of the aged heart, but the molecular mechanism of the aging-associated cardiac remodeling has not been well elucidated.The increasing evidence shows that non-coding RNAs participate in the pathology of the aging-associated cardiac remodeling. We observed that circular RNA circRNA_000203 was up-regulated in the myocardium of D-galactose–induced aged mouse. Over-expression of circRNA_000203 could significantly enhance the hypertrophic phenotype in mouse cardiomyocytes and enhance the fibrotic phenotype in mouse myofibroblasts, respectively. The results of dual luciferase assay and RNA pull-down assay revealed the specific interaction between circRNA_000203 and miR-26b. We hypothesize that circRNA_000203 sponges miR-26b and derepresses the downstream target genes of miR-26b, including Col1a2、CTGF、MEF2C、CCND1，-2，CCNE1 and CDK6, contributing to cardiac fibrosis and cardiac hypertrophy. The transgenic circRNA_000203 mice and the wild type control mice, and neonatal mouse cardiomyocytes and cardiac fibroblasts derived from the above two kinds of mice will be utilized in the present project. We will demonstrate the mechanism underlying the enhancement of the aging-associated cardiac remodeling by circRNA_000203 at the whole organism,cultural vessel,cellular and molecular level, respectively. The present study is expected to provide scientific evidence and material for developing new therapeutic approaches based on circRNAs for the aging-associated cardiac remodeling.