CCRR regulate MYZAP-PKP2-Nav1.5 signaling pathway in atrial fibrillation following myocardial infarction

iScience. 2024 Oct 5;27(11):111102. doi: 10.1016/j.isci.2024.111102. eCollection 2024 Nov 15.

Abstract

Atrial fibrillation (AF) is the most common sustained arrhythmia which brings a heavy burden to the lives and health of patients worldwide. Our earlier research documented cardiac conduction regulatory RNA (CCRR) as an antiarrhythmic lncRNA in heart failure. Here, we report that CCRR was decreased in atrial tissue after MI, MYZAP, and Nav1.5 were increased in the atrium in cardiac-specific transgenic CCRR overexpression mice. Overexpression of CCRR carried by AAV-9 reversed the incidence and duration of AF and atrial conduction velocity in MI mice. MYZAP overexpression reversed the decreasing levels of PKP2, Nav1.5, and AF incidence after MI in addition to downregulating the expression levels of TLR2, TLR4, and inflammation-related factors following MI. Our work revealed that CCRR can improve the occurrence and development of AF after MI through the MYZAP-PKP2 pathway and inhibit Nav1.5 and TLR signaling pathways associated with inflammation, thus serving as a therapeutic target for AF.

Keywords: Biological sciences; Molecular biology; Pathophysiology.