LRP6-mediated phosphorylation of connexin43 in myocardial infarction

Xu-Min Zhang; Ya-Ling Liu; Ying Cai; Ying Hao; Sheng Kang

doi:10.1016/j.isci.2023.106160

LRP6-mediated phosphorylation of connexin43 in myocardial infarction

iScience. 2023 Feb 8;26(3):106160. doi: 10.1016/j.isci.2023.106160. eCollection 2023 Mar 17.

Authors

Xu-Min Zhang¹, Ya-Ling Liu², Ying Cai¹, Ying Hao¹, Sheng Kang¹

Affiliations

¹ Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Jimo Road 150, Shanghai 200120, China.
² Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Pujian Road 160, Shanghai 200127, China.

Abstract

Ventricular tachycardia (VT) and ventricular fibrillation are most causes of early death in patients with acute myocardial infarction (AMI). Conditional cardiac-specific low-density lipoprotein receptor-related protein 6 (LRP6)-knockout mice with connexin 43 (Cx43) reduction triggered the lethal ventricular arrhythmias. Thus, it is necessary for exploring whether LRP6 and its upstream genes circRNA1615 mediate the phosphorylation of Cx43 in VT of AMI. Here, we showed that circRNA1615 regulated the expression of LRP6 mRNA through sponge adsorption of miR-152-3p. Importantly, LRP6 interference fragments aggravated hypoxia injury of Cx43, while overexpression of LRP6 improved the phosphorylation of Cx43. Subsequently, interference with G-protein alpha subunit (Gα_s) downstream of LRP6 further inhibited the phosphorylation of Cx43, along with increasing VT. Our results demonstrated that LRP6 upstream genes circRNA1615 controlled the damage effect and VT in AMI, and LRP6 mediated the phosphorylation of Cx43 via Gα_s which played a role in VT of AMI.

Keywords: Biochemistry; Biological sciences; Cell biology; Molecular biology.