Exosomal Long Noncoding RNA H19 as a Biomarker and Therapeutic Target in Atrial Fibrillation

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Biomarker Discovery

Background:

• Exosomal long noncoding RNAs (lncRNAs) are implicated in disease but their role in atrial fibrillation (AF) is unknown.
• Identifying novel biomarkers and therapeutic targets for AF is crucial for improving patient outcomes.

Purpose of the Study:

• To identify AF-specific serum exosomal lncRNAs.
• To investigate the role of identified lncRNAs in AF pathophysiology.
• To evaluate their potential as theragnostic targets for AF.

Main Methods:

• RNA sequencing and quantitative reverse transcription PCR (qRT-PCR) on serum exosomes.
• In vitro loss- and gain-of-function studies in angiotensin II (Ang II)-treated iPSC-derived atrial cardiomyocytes.
• In vivo cardiac-specific overexpression of lncRNA H19 in a mouse model.
• Mechanistic investigation involving microRNA (miRNA) sponging and pathway analysis.

Main Results:

• lncRNA H19 was significantly downregulated in serum exosomes of AF patients.
• Serum exosomal lncRNA H19 levels demonstrated diagnostic validity for AF.
• H19 modulated Ang II-induced cardiac hypertrophy in vitro and in vivo.
• H19 acts as a sponge for miR-141-3p and miR-200a-3p, regulating the PTEN pathway.

Conclusions:

• Circulating exosomal lncRNA H19 is a novel diagnostic biomarker for AF.
• lncRNA H19 plays a critical role in cardiac hypertrophy and AF development.
• Exosomal lncRNA H19 presents a promising theragnostic target for AF.