Circulating circRNA as biomarkers for dilated cardiomyopathy etiology

Abstract

Dilated cardiomyopathy (DCM) is the third most common cause of heart failure. The multidisciplinary nature of testing ¿ involving genetics, imaging, or cardiovascular techniques ¿ makes its diagnosis challenging. Novel and reliable biomarkers are needed for early identifcation and tailored personalized management. Peripheral circular RNAs (circRNAs), a leading research topic, remain mostly unexplored in DCM. We aimed to assess whether peripheral circRNAs are expressed diferentially among etiology-based DCM. The study was based on a case¿control multicentric study. We enrolled 130 subjects: healthy controls (n=20), idiopathic DCM (n=30), ischemic DCM (n=20), and familial DCM patients which included pathogen variants of (i) LMNA gene (n=30) and (ii) BCL2-associated athanogene 3 (BAG3) gene (n=30). Diferentially expressed circRNAs were analyzed in plasma samples by quantitative RT-PCR and cor¿ related to relevant systolic and diastolic parameters. The patho¿ physiological implications were explored through bioinformatics tools. Four circRNAs were overexpressed compared to controls: hsa_circ_0003258, hsa_circ_0051238, and hsa_circ_0051239 in LMNA-related DCM and hsa_circ_0089762 in the ischemic DCM cohort. The obtained areas under the curve confrm the discriminative capacity of circRNAs. The circRNAs correlated with some diastolic and systolic echocardiographic parameters with notable diagnostic potential in DCM. Circulating circRNAs may be helpful for the etiology-based diagnosis of DCM as a non-invasive biomarker.