Circular RNA CHACR is involved in the pathogenesis of cardiac hypertrophy

Background: Circular RNAs (circRNAs) exhibit differential expression in cardiac hypertrophy; however, their functions and mechanisms remain largely unexplored.This study aimed to determine the involvement of circRNAs in the pathogenesis of myocardial hypertrophy.Methods: A mouse model of cardiac hypertrophy was established using transverse aortic constriction (TAC) and differentially expressed circRNAs were identified via high-throughput sequencing.To facilitate gene overexpression or knockdown, related viruses were injected into myocardial tissues of the mice.Cardiomyocyte hypertrophy was assessed using quantitative real-time PCR and immunofluorescence staining.RNA immunoprecipitation, RNA pull-down assay and fluorescence in situ hybridization were conducted to confirm the interaction between circRNAs and proteins.Protein expression and degradation were evaluated using cycloheximide-chase assay, immunoprecipitation, and western blotting.Results: Cardiac hypertrophy-associated circRNA (CHACR) was significantly downregulated in myocardial tissues from TAC mice.CHACR can attenuate cardiac hypertrophy through upregulating carnitine palmitoyltransferase-1b (CPT1b) expression.Mechanistically, CHACR directly interacted with CPT1b and decreased its protein degradation by inhibiting the ubiquitin-proteasome pathway to increase its expression in cardiomyocytes.Moreover, CPT1b overexpression decreased L-carnitine levels and inhibited the Jak2/Stat3 signaling pathway, which was associated with the pathogenesis of myocardial hypertrophy.Conclusions: CHACR attenuated cardiomyocyte hypertrophy by facilitating the expression of CPT1b, which plays a role in regulating the Jak2/Stat3 pathway via L-carnitine.CHACR may thus be a potential therapeutic target for pathological myocardial hypertrophy.