Circular RNA CHACR is involved in the pathogenesis of cardiac hypertrophy

<b>Background:</b> 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. <b>Methods:</b> 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 <i>in situ</i> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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.