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Updated: May 8, 2025
Author Spotlight: Advancing the Analysis of Plasma Extracellular Vesicle Proteome for Cardiovascular Biomarker Studies
Published on: January 31, 2025
Differential Expression Spectrum of circRNA in Plasma Exosomes in Dilated Cardiomyopathy With Heart Failure
Shuai Xu1,2,3,4,5, Ge Zhang1,2,3, Xin Tan4,5
1Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Insights
Dilated cardiomyopathy (DCM) is linked to specific circular RNA (circRNA) patterns in plasma exosomes. These findings may improve diagnostic methods for heart failure patients.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- Dilated cardiomyopathy (DCM) is a major cause of heart failure and mortality.
- Current diagnostic tools for DCM, like echocardiography and MRI, lack specificity.
- Exosomes mediate intercellular communication, and their cargo, including circular RNAs (circRNAs), influences cellular functions.
Purpose of the Study:
- To investigate plasma exosomal circRNA profiles in patients with DCM and chronic heart failure (CHF).
- To identify novel circRNAs associated with DCM and CHF pathophysiology.
- To explore the potential of exosomal circRNAs as diagnostic biomarkers for DCM.
Main Methods:
- Next-generation sequencing was used to analyze plasma exosomal circRNA expression.
- Profiles from DCM patients with CHF were compared to those of healthy controls.
- Bioinformatic analysis identified differentially expressed circRNAs and associated pathways.
Main Results:
- Distinct circRNA expression patterns were observed in DCM patients with CHF.
- Forty-nine unique circRNAs were identified in the plasma exosomes of the DCM cohort.
- These circRNAs were linked to pathways involved in extracellular ligand sequestration, acetylation, and endocytosis.
Conclusions:
- Plasma exosomal circRNAs exhibit unique expression profiles in DCM with CHF.
- These findings offer insights into DCM's underlying mechanisms.
- Exosomal circRNAs show promise as potential biomarkers for improving DCM diagnosis.
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.
