Differential expressions of exosomal miRNAs in patients with chronic heart failure and hyperuricemia: diagnostic values of miR-27a-5p and miR-139-3p.
10.12122/j.issn.1673-4254.2025.01.06
- Author:
Zhiliang CHEN
1
;
Yonggang YANG
2
;
Xia HUANG
1
;
Yan CHENG
3
;
Yuan QU
4
;
Qiqi HENG
5
;
Yujia FU
5
;
Kewei LI
5
;
Ning GU
1
Author Information
1. Department of Cardiology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210022, China.
2. Clinical Laboratory, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210022, China.
3. Department of Pharmacy, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210022, China.
4. Department of Emergency Medicine, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210022, China.
5. Nanjing University of Chinese Medicine, Nanjing 210023, China.
- Publication Type:Journal Article
- Keywords:
AMP-activated protein kinases;
TOR serine-threonine kinases;
autophagy;
chronic heart failure;
exosomes;
hyperuricemia;
microRNAs
- MeSH:
Humans;
Hyperuricemia/diagnosis*;
Heart Failure/genetics*;
MicroRNAs/metabolism*;
Exosomes/metabolism*;
Chronic Disease;
Male;
Female;
Middle Aged;
Animals
- From:
Journal of Southern Medical University
2025;45(1):43-51
- CountryChina
- Language:English
-
Abstract:
OBJECTIVES:To analyze the differentially expressed exosomal miRNAs in patients with chronic heart failure (CHF) complicated by hyperuricemia (HUA) and explore their potential as novel diagnostic molecular markers and their target genes.
METHODS:This study was conducted among 30 CHF patients with HUA (observation group) and 30 healthy volunteers (control group) enrolled between September, 2020 and September, 2023. Peripheral blood samples were collected from 6 CHF patients with HUA for analyzing exosomal miRNAs by high-throughput sequencing, and the results were validated in the remaining 24 patients using qRT-PCR. GO and KEGG enrichment analyses were performed to predict the the target genes of the identified differential miRNAs. We also validated the differentially expressed miRNAs by animal experiment.
RESULTS:A total of 42 differentially expressed exosomal miRNAs were detected in observation group by high-throughput sequencing; among them, miR-27a-5p was significantly upregulated (P=0.000179), and miR-139-3p was significantly downregulated (P=0.000058). In the 24 patients with both CHF and PUA, qRT-PCR validated significant upregulation of miR-27a-5p (P=0.004) and downregulation of miR-139-3p (P=0.005) in serum exosomes. When combined, miR-27a-5p and miR-139-3p had a maximum area under the curve (AUC) of 0.899 (95% CI: 0812-0.987) for predicting CHF complicated by HUA. GO and KEGG enrichment analyses suggested that the differential expressions of miR-27a-5p and miR-139-3p was associated with the activation of the AMPK-mTOR signaling pathway to activate the autophagic response. We obtained the same conclusion from animal experiment.
CONCLUSIONS:Upregulated exosomal miR-27a-5p combined with downregulated exosomal miR-139-3p expression can serve as a novel molecular marker for diagnosis of CHF complicated by HUA, and their differential expression may promote autophagy in cardiomyocytes by activating the AMPK-mTOR signaling pathway.
