环状RNA CHACR通过促进CPT1b表达抑制心肌肥厚的机制研究

中国高血压患者约2.45亿，心肌肥厚（CH）是高血压患者常见的病理特征，至今病理机制不清。我们前期研究证实，circHIPK3作为ceRNA，通过抑制miR-29b-3p上调Col1a1和Col3a1的表达，导致糖尿病心肌纤维化增加。预实验结果：通过circRNAs高通量测序发现CHACR在CH心肌组织中明显下调；CHACR过表达可下调AngII诱导的心肌肥厚标志物升高及表面积的增大；质谱发现CHACR与CPT1b结合紧密，且有文献发现CPT1b功能受损可以导致脂肪酸在胞质蓄积引起CH。我们提出CHACR过表达可以促进CPT1b抑制AngII诱导的CH。本项目将应用荧光定量PCR、Western Blot、免疫荧光和质谱分析等多种实验方法，结合CH小鼠模型，解析CHACR上调CPT1b抑制CH的分子机制。通过干预CHACR调节CPT1b来治疗CH，这将为CH的病理机和治疗提供指导和新思路。

There are about 245 million patients with hypertension in China. Myocardial hypertrophy ((CH)) is a common pathological feature in patients with hypertension, but the pathological mechanism is still unclear. Our previous studies confirmed that circHIPK3 as a ceRNA, inhibits the upregulation of Col1a1 and Col3a1 expression by miR-29b-3p, resulting in an increase in diabetic myocardial fibrosis. Pre-experimental results: through circRNAs high-throughput sequencing, it was found that CHACR was significantly down-regulated in CH myocardium; overexpression of CHACR could down-regulate the increase of cardiac hypertrophy markers and surface area induced by AngII; mass spectrometry showed that CHACR was closely bound to CPT1b, and some literature found that impaired CPT1b function could lead to CH caused by fatty acid accumulation in the cytoplasm. We suggest that overexpression of CHACR can promote CPT1b to inhibit AngII-induced CH. In this project, fluorescence quantitative PCR, Western Blot, immunofluorescence and mass spectrometry and other experimental methods, combined with CH mouse model, were used to analyze the molecular mechanism of CHACR up-regulating CPT1b and inhibiting CH. The treatment of CH, by interfering with CHACR regulating CPT1b will provide guidance and new ideas for the pathogenesis and treatment of CH.