Circular RNA CircFndc3b modulates cardiac repair after myocardial infarction via FUS/VEGF-A axis

Venkata Naga Srikanth Garikipati, Suresh Kumar Verma, Zhongjian Cheng, Dongming Liang, May M. Truongcao, Maria Cimini, Yujia Yue, Grace Huang, Chunlin Wang, Cindy Benedict, Yan Tang, Vandana Mallaredy, Jessica Ibetti, Laurel Grisanti, Sarah M. Schumacher, Erhe Gao, Sudarsan Rajan, Jeremy E. Wilusz, David Goukassian, Steven R. HouserWalter J. Koch, Raj Kishore

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276 Scopus citations


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.

Original languageEnglish
Article number4317
JournalNature Communications
Issue number1
StatePublished - 1 Dec 2019


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