Differential Expression Spectrum of circRNA in Plasma Exosomes in Dilated Cardiomyopathy With Heart Failure

Abstract

Dilated cardiomyopathy (DCM), a form of non-ischaemic myocardial disease, is characterised by structural and functional cardiac abnormalities. As defined by the World Health Organisation, DCM constitutes a significant cardiac pathology, leading to increased morbidity and mortality due to complications such as heart failure and arrhythmias. The diagnostic process for DCM predominantly employs echocardiography and MRI, with biomarkers like NT-pro BNP and troponin providing supportive, yet non-specific, evidence. Exosomes, small extracellular vesicles, play a critical role in intercellular communications by transferring biomolecules including lipids, proteins, messenger RNA (mRNA) and non-coding RNA (ncRNA) to target cells, thereby influencing key cellular processes such as proliferation, differentiation, apoptosis, angiogenesis and immune modulation. Within the ncRNA category, circular RNAs (circRNAs) are notable for their cellular specificity and evolutionary conservation and are often implicated in the regulatory mechanisms underlying DCM and heart failure. This investigation employed next-generation sequencing technology to analyse plasma exosomal circRNA profiles in DCM patients with chronic heart failure (CHF), compared to healthy controls. The analysis revealed distinct circRNA expression patterns, identifying 49 uniquely expressed circRNAs in the DCM cohort with CHF. These circRNAs were associated with several critical biological pathways, including the sequestration of extracellular ligands from receptors, N-acetyltransferase activity, histone acetyltransferase activity and endocytic vesicle membrane composition. The findings of this study provide valuable insights into the pathophysiological mechanisms of DCM and offer evidence for improving clinical diagnostic methodologies.

Keywords: circRNA; dilated cardiomyopathy; heart failure; plasma exosomal.