Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19140, USA.
Division of Cardiovascular Diseases, Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
Nat Commun. 2019 Sep 20;10(1):4317. doi: 10.1038/s41467-019-11777-7.
Circular RNAs are generated from many protein-coding genes, but their role in cardiovascular health and disease states remains unknown. Here we report identification of circRNA transcripts that are differentially expressed in post myocardial infarction (MI) mouse hearts including circFndc3b which is significantly down-regulated in the post-MI hearts. Notably, the human circFndc3b ortholog is also significantly down-regulated in cardiac tissues of ischemic cardiomyopathy patients. Overexpression of circFndc3b in cardiac endothelial cells increases vascular endothelial growth factor-A expression and enhances their angiogenic activity and reduces cardiomyocytes and endothelial cell apoptosis. Adeno-associated virus 9 -mediated cardiac overexpression of circFndc3b in post-MI hearts reduces cardiomyocyte apoptosis, enhances neovascularization and improves left ventricular functions. Mechanistically, circFndc3b interacts with the RNA binding protein Fused in Sarcoma to regulate VEGF expression and signaling. These findings highlight a physiological role for circRNAs in cardiac repair and indicate that modulation of circFndc3b expression may represent a potential strategy to promote cardiac function and remodeling after MI.
环状 RNA 可由许多蛋白编码基因产生，但它们在心血管健康和疾病状态中的作用尚不清楚。在这里，我们报告了在心肌梗死后（MI）小鼠心脏中差异表达的环状 RNA 转录本的鉴定，包括circFndc3b，其在 MI 后心脏中显著下调。值得注意的是，人类 circFndc3b 同源物在缺血性心肌病患者的心脏组织中也显著下调。在心脏内皮细胞中过表达 circFndc3b 可增加血管内皮生长因子-A 的表达，并增强其血管生成活性，减少心肌细胞和内皮细胞凋亡。腺相关病毒 9 介导的心肌梗死后心脏中 circFndc3b 的过表达可减少心肌细胞凋亡，增强新生血管形成并改善左心室功能。从机制上讲，circFndc3b 与肉瘤融合蛋白相互作用，以调节 VEGF 的表达和信号。这些发现强调了环状 RNA 在心脏修复中的生理作用，并表明调节 circFndc3b 的表达可能是一种促进 MI 后心脏功能和重塑的潜在策略。
Zotero 插件
