Hsa-circ-ACSL1 Enhances Apoptosis and Autophagy in Myocarditis Cardiomyocytes Through the miR-7-5p/XBP1 Axis.

Abstract

Viral myocarditis (VMC) is a common cardiovascular disease, and circular RNAs (circRNAs) have been identified to play an important role in the pathophysiology of cardiovascular disease. However, the clinical significance, biological functions, and regulatory mechanisms of circRNAs in VMC remain poorly understood. Therefore, this study explored the biological functions and regulatory mechanisms of circ-ACSL1 in VMC. The animal and cell models of VMC were established by infecting BABL/C mice and interleukin-2 cells with coxsackievirus B3 (CVB3). Pro-inflammatory factors, markers of myocardial injury, apoptosis, and autophagy were detected to evaluate the degree of myocardial inflammation and myocardial injury after altering circ-ACSL1, microRNA-7-5p (miR-7-5p), and X-box binding protein 1 (XBP1) expression alone or in combination. Knocking down circ-ACSL1 could inhibit inflammation, autophagy, and apoptosis in VMC animals and cells. Mechanistically, circ-ACSL1 targeted miR-7-5p to regulate the downstream target XBP1. In addition, depleting miR-7-5p rescued the therapeutic effect of depleting circ-ACSL1. Overexpression of circ-ACSL1 aggravated VMC; however, this effect was saved by knocking down XBP1. By competitively absorbing miR-7-5p, circ-ACSL1 increases XBP1 expression and aggravates myocardial inflammation. Meaningfully, VMC treatment may benefit from circ-ACSL1 as a potential biomarker for precise diagnosis and as a potential therapeutic target.