Open Access

ARTICLE

Dynamic Plasma Exosomal miRNA Profiling Uncovers Molecular Trajectories of Cardiac Repair following Cone Reconstruction for Ebstein’s Anomaly

Jiaxiong Wu^1,2,3,#, Runzhang Liang^1,#, Naijimuding ABUDUREXITI^4,#, Jing Ling², Zirui Peng², Jinxin Li¹, Canxin Wang¹, Yong Zhang¹, Haiyun Yuan^1,2,3,*, Shusheng Wen^1,2,3,*
1 Department of Cardiac Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China
2 Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
3 Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangzhou, China
4 Department of Cardiovascular Surgery, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
* Corresponding Author: Haiyun Yuan. Email: ; Shusheng Wen. Email:
# These authors contributed equally to this work
(This article belongs to the Special Issue: Novel Insights into Congenital Heart Disease: Pathophysiology, Biomarkers, and Future Directions)

Structural and Congenital Heart Disease https://doi.org/10.32604/schd.2026.077455

Received 09 December 2025; Accepted 20 April 2026; Published online 02 June 2026

Abstract

Objective: Cone reconstruction (CR) is the preferred surgical treatment for Ebstein’s anomaly (EA). However, the molecular mechanisms underlying postoperative cardiac repair remain unclear. This study investigated the dynamic changes of plasma exosomal microRNAs (miRNAs) in EA patients before and after CR, exploring their association with postoperative cardiac function recovery and potential molecular mechanisms. Methods: Plasma samples were collected from 10 EA patients undergoing CR preoperatively, 1 day postoperatively, and 7 days postoperatively, along with samples from 10 healthy controls. Plasma exosomes were isolated using size-exclusion chromatography. Exosomal miRNAs were extracted and sequenced, followed by differential expression, functional enrichment, time-series clustering, and correlation analyses with clinical parameters. Results: Typical exosomes and miRNA profiles were identified. Preoperatively, EA patients exhibited distinct exosomal miRNA signatures enriched in pathways related to cardiac development, extracellular matrix remodeling, and apoptosis regulation. On postoperative day 1, miRNAs associated with inflammation and myocardial stress (miR-208a-3p, miR-208b-3p, and miR-499a-5p) were upregulated. By postoperative day 7, molecular pathways shifted toward structural remodeling and functional recovery, involving extracellular matrix organization and heart contraction regulation. Time-series clustering delineated an ordered molecular cascade associated with acute stress responses and structural remodeling. Five miRNAs persistently downregulated in the EA group were identified, potentially involved in key pathological processes including epigenetic regulation, metabolic processes, and muscle development. Notably, miR-224-5p, miR-548as-5p, and miR-30c-5p were significantly associated with right ventricular fractional area change, while miR-338-3p correlated with N-terminal pro-B-type natriuretic peptide dynamics. Conclusion: This study provides the first comprehensive dynamic landscape of plasma exosomal miRNAs in EA patients undergoing CR, with temporally coordinated molecular characteristics related to acute stress protection, structural remodeling, and functional recovery. Key miRNAs (miR-224-5p, miR-30c-5p, and miR-338-3p) may serve as potential molecular biomarkers and therapeutic targets for postoperative cardiac recovery, offering new insights into the molecular basis of CR-mediated cardiac repair in EA.

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Keywords

Congenital heart disease; Ebstein’s anomaly; Cone reconstruction; exosomes; microRNAs

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