Circular RNA Foxo3 in cardiac ischemia-reperfusion injury in heart transplantation: A new regulator and target.

Abstract

Ischemia-reperfusion (I/R) injury occurring in heart transplantation (HT) remains as a leading cause of transplant heart graft failure. Circular RNAs (circRNAs) play important roles in gene regulation and diseases. However, the impact of circRNAs on I/R injury during HT remains unknown. This study aims to investigate the role of circular RNA Foxo3 (circFoxo3) in I/R injury in HT. Using an in vivo mouse HT model and an in vitro cardiomyocyte culture model, we demonstrated that circFoxo3 is significantly upregulated in I/R-injured hearts and hypoxia/reoxygenation (H/R)-damaged cardiomyocytes. Knockdown of circFoxo3 using siRNA not only reduces cell apoptosis and death, mitochondrial damage, and expression of apoptosis/death-related genes in vitro, but also protects heart grafts from prolonged cold I/R injury in HT. We also show that circFoxo3 interacts with Foxo3 proteins and inhibits the phosphorylation of Foxo3 and that it indirectly affects the expression of miR-433 and miR-136. In conclusion, circRNA is involved in I/R injury in HT and knockdown of circFoxo3 with siRNA can reduce I/R injury and improve heart graft function through interaction with Foxo3. This study highlights that circRNA is a new type of molecular regulator and a potential target for preventing I/R injury in HT.

• Authors: Yale Su, Cuilin Zhu, Bowen Wang, Hao Zheng, Vivian McAlister, James C Lacefield, Douglas Quan, Tina Mele, Adam Greasley, Kexiang Liu, Xiufen Zheng
• Journal: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (Am J Transplant) Vol. 21 Issue 9 Pg. 2992-3004 (09 2021) ISSN: 1600-6143 [Electronic] United States
• PMID: 33382168 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.

Chemical References

• MicroRNAs
• RNA, Circular

Topics

• Animals
• Apoptosis
• Heart Transplantation (adverse effects)
• Mice
• MicroRNAs (genetics)
• Myocytes, Cardiac
• RNA, Circular
• Reperfusion Injury