CircMap4k2 reactivated by aneurysm plication alleviates residual cardiac remodeling after SVR by enhancing cardiomyocyte proliferation in post-MI mice

• DOI: 10.1016/j.jare.2023.11.034
• Publication Date: 2023-12-02T16:20:29Z
• Authors: Junyu Yan; Chenzhi Ai; Qi Chen; Qiuhan Wang; Yingqi Zhu; Mingjue Li; Kaitong Chen; Mingyuan He; Mengjia Shen; Lu Chen; Rui Zhang; Cankun Zheng; Wangjun Liao; Jianping Bin; Hairuo Lin; Siyuan Ma; Ning Tan; Yulin Liao
• Keywords: Ventricular remodeling; Ventricular aneurysm

Surgical ventricular reconstruction (SVR) is an alternative therapeutic approach in patients with refractory heart failure (HF), but residual remodeling after SVR limits the improvement of HF. Recently, we reported that may act as environmental cue to reactivate endogenous proliferation cardiomyocytes; however, it unclear whether enhancing cardiomyocyte regeneration further improves HF SVR. We aimed explore circular RNAs (circRNAs) would involved and their mechanisms. Male C57BL/6 mice were subjected myocardial infarction (MI) or sham surgery. Four weeks later, MI a large aneurysm underwent second open-chest operation only. Echocardiography histological analysis used evaluate function, cardiac remodeling, regeneration. Sequencing RNAs, RNA immunoprecipitation, pulldown, luciferase reporter assay underlying markedly attenuated induced regeneration, evidenced by positive staining Ki-67, phospho-histone H3 (pH3), Aurora B plication zone, significant still existed comparison group. results showed altered expression profile circRNAs, circMap4k2 was identified most upregulated one. After characterizing circMap4k2, noted overexpression significantly promoted cardiomyocytes cultured neonatal rat silencing inhibited it; similar obtained SVR-treated not without treatment. Residual overexpression. CircMap4k2 bound miR-106a-3p targeting downstream effector antizyme inhibitor 1 (Azin1) gene. acts targets miR-106a-3p/Azin1 pathway increase zone attenuate