# Differential expression profiles of plasma exosomal microRNAs in dilated cardiomyopathy with chronic heart failure

Researcher: Ge Zhang
Chinese name: 张格
ORCID identity anchor: https://orcid.org/0000-0002-3116-3246
Canonical researcher: https://drgezhang.com/#person

Journal: Journal of Cellular and Molecular Medicine
Year: 2023
Type: Article
DOI: 10.1111/jcmm.17789
Canonical page: https://drgezhang.com/papers/doi-10-1111-jcmm-17789.html
Markdown record: https://drgezhang.com/papers/doi-10-1111-jcmm-17789.md

## Full Authors

1. Li Zhang
2. Ge Zhang
3. Yongzheng Lu
4. Jiamin Gao
5. Zhen Qin
6. Shuai Xu
7. Zeyu Wang
8. Yanyan Xu
9. Yu Yang
10. Jinying Zhang
11. Junnan Tang

## Official Abstract

As one of the most prevalent heritable cardiovascular diseases, dilated cardiomyopathy (DCM) induces cardiac insufficiency and dysfunction. Although genetic mutation has been identified one of the causes of DCM, the usage of genetic biomarkers such as RNAs for DCM early diagnosis is still being overlooked. In addition, the alternation of RNAs could reflect the progression of the diseases, as an indicator for the prognosis of patients. Therefore, it is beneficial to develop genetic based diagnostic tool for DCM. RNAs are often unstable within circulatory system, leading to the infeasibility for clinical application. Recently discovered exosomal miRNAs have the stability that is then need for diagnostic purpose. Hence, fully understanding of the exosomal miRNA within DCM patients is vital for clinical translation. In this study, we employed the next generation sequencing based on the plasma exosomal miRNAs to comprehensively characterize the miRNAs expression in plasma exosomes from DCM patients exhibiting chronic heart failure (CHF) compared to healthy individuals. A complex landscape of differential miRNAs and target genes in DCM with CHF patients were identified. More importantly, we discovered that 92 differentially expressed miRNAs in DCM patients undergoing CHF were correlated with several enriched pathways, including oxytocin signalling pathway, circadian entrainment, hippo signalling pathway‐multiple species, ras signalling pathway and morphine addiction. This study reveals the miRNA expression profiles in plasma exosomes in DCM patients with CHF, and further reveal their potential roles in the pathogenesis of it, presenting a new direction for clinical diagnosis and management of DCM patients with CHF.

Text reproduced verbatim from PMC ([source](https://pmc.ncbi.nlm.nih.gov/articles/PMC10339102/)); [DOI](https://doi.org/10.1111/jcmm.17789); [CC-BY-4.0](https://creativecommons.org/licenses/by/4.0/).

<a id="paper-discovery"></a>
## Research & review context

### Research fields

- Extracellular-vesicle biomarker research
- Dilated cardiomyopathy and heart failure

### Review topics

- Circulating RNA biomarkers in cardiomyopathy
- Human plasma exosomal microRNA profiling

### Scientific role

Exploratory human DCM-HF plasma exosomal microRNA profiling with small external expression-assay follow-up.

### Evidence position

Human case-control biomarker evidence; not prospective diagnosis, therapeutic RNA delivery or external miR-185-5p validation in this article.

### Related concepts

- Vesicle-associated RNA candidates
- Discovery versus assay follow-up

### Possible citation contexts

- Background: extracellular vesicles as sources of candidate heart-failure biomarkers.
- Evidence synthesis: human circulating microRNA expression studies in DCM-HF, separate from preclinical miRNA interventions.

Possible literature-review contexts, not evidence of existing citations. Read the findings and Evidence Scope before citing the original article.

## Evidence Scale

**Differential expression profiles of plasma exosomal microRNAs in dilated cardiomyopathy with chronic heart failure**

Human plasma exosomal miRNA profiling in DCM with chronic heart failure identified an article-reported 92-feature differential set, computational target networks and external qRT-PCR assessment of 10 hub miRNAs in 10 patients and 6 controls.

| Evidence | Value |
| --- | --- |
| Sequencing feature landscape | 3,687 article-reported miRNA features |
| Final differential feature set | 92 features: 48 upregulated and 44 downregulated |
| External qRT-PCR participants | 10 DCM patients and 6 healthy controls |
| External assay panel | 10 selected hub miRNAs |

### Counting note

Discovery and external assay phases are distinct. The discovery participant count is not reliably established from the reviewed text, so no complete unique-participant total is inferred. Sequencing features, predicted genes, network nodes and qRT-PCR technical triplicates are not additional participants. External validation here means a small external expression-assay comparison, not validation of a clinical diagnostic or prognostic tool.

## Research Question

Which plasma exosomal miRNA expression patterns distinguish the studied DCM-with-chronic-heart-failure samples from healthy controls, and which candidate signals were evaluated by an external assay?

## Author Evidence Summary

This human case-control molecular-profiling study used plasma vesicle preparations, small-RNA sequencing, target prediction and external qRT-PCR to investigate DCM with chronic heart failure. The Results report 92 differentially expressed miRNA features, comprising 48 upregulated and 44 downregulated features under the stated screening thresholds. Computational enrichment and network analyses provide biological hypotheses rather than directly measured target regulation. Ten selected hub miRNAs were assessed in an external group of 10 patients and 6 healthy controls, with expression-profile separation reported. The discovery participant count was not reliably established from the reviewed text and is not reconstructed here. miR-185-5p appears in the discovery table and predicted network, but not in the listed 10-miRNA external qRT-PCR panel. The evidence supports exploratory circulating-RNA associations and assay follow-up, not an early-detection test, prospective prognosis or a human causal mechanism.

## Key Findings

<a id="kf1"></a>
### KF1: The study combined human DCM-HF plasma miRNA discovery with a separate external expression-assay comparison.

Context: Human disease-versus-healthy comparison; no prospective clinical intervention.

| Evidence | Value |
| --- | --- |
| Disease phenotype | DCM with chronic heart failure |
| Discovery assay | Small-RNA library sequencing on Illumina HiSeq2500 |
| External qRT-PCR sample | 10 DCM patients; 6 healthy controls |

Source locator: Methods 2.1, 2.8 and 2.9; Results 3.10; Fig. 6

<a id="kf2"></a>
### KF2: The isolated plasma preparations showed vesicle morphology, size and marker findings consistent with the reported exosomal preparation.

Context: The authors use the term exosomes; these measurements alone do not establish cardiac cell of origin or exclusive endosomal origin.

| Evidence | Value |
| --- | --- |
| Isolation | ExoQuick precipitation |
| Median particle diameter | Approximately 81 nm in the reported groups |
| Marker findings | CD63 and CD81 detected; Calnexin not detected |

Source locator: Methods 2.3-2.6; Results 3.1; Fig. 1B-D

<a id="kf3"></a>
### KF3: The Results identify 92 differential miRNA features after the stated fold-change and P-value screen.

Context: The Results threshold is reported here; the Fig. 3A caption instead prints 0.05 for the absolute-logFC threshold, an unresolved reporting difference.

| Evidence | Value |
| --- | --- |
| Detected miRNA features | 3,687 |
| Final threshold as stated in Results | Absolute logFC >0.5 and P<0.05 |
| Final differential features | 92 |
| Upregulated / downregulated | 48 / 44 |

Source locator: Results 3.2; Table 1; Figs. 2 and 3A

<a id="kf4"></a>
### KF4: Target prediction and network analysis connected differential miRNA features to candidate regulatory and pathway contexts.

Context: Computational relationships do not demonstrate direct miRNA binding, altered target-protein abundance or pathway causality.

| Evidence | Value |
| --- | --- |
| miRNA-mRNA network | 55 nodes: 32 miRNAs and 23 hub genes |
| Network edges | 59 |
| Enrichment examples | Circadian entrainment, oxytocin signaling and Hippo-related pathways |

Source locator: Methods 2.10-2.12; Results 3.3-3.9; Figs. 3-5

<a id="kf5"></a>
### KF5: External qRT-PCR and multivariate expression comparisons assessed a 10-miRNA hub panel in a small independent population.

Context: Assay-level follow-up and expression-profile separation; not a validated diagnostic operating threshold or prospective clinical performance.

| Evidence | Value |
| --- | --- |
| External sample | 10 DCM patients and 6 healthy controls |
| Hub miRNAs tested | 10 |
| Readouts | qRT-PCR, Euclidean expression distance and PCoA |

Source locator: Methods 2.9, 2.13 and 2.14; Results 3.10; Fig. 6

<a id="kf6"></a>
### KF6: miR-185-5p was a discovery-stage signal and predicted-network candidate, rather than a member of the reported external 10-miRNA panel.

Context: This distinction matters when connecting this observational article with later miR-185-5p intervention research.

| Evidence | Value |
| --- | --- |
| Table 1 hsa-miR-185-5p logFC | 1.04 |
| Table 1 hsa-miR-185-5p P value | 0.0322 |
| External 10-miRNA panel membership | Not included in the listed qRT-PCR panel |

Source locator: Table 1; Results 3.9-3.10; Methods 2.9

## Study Design & Analytical Framework

### Study profile

- Study Design: Human case-control plasma exosomal miRNA discovery with external qRT-PCR follow-up
- Evidence Type: Human molecular association and small external assay evaluation
- Population: Patients with DCM and chronic heart failure compared with healthy individuals; recruitment criteria included LVEF <=45%, NYHA II-IV and heart-failure history longer than 6 months
- Primary Endpoint: Between-group plasma exosomal miRNA expression differences
- Secondary Endpoint: Predicted target/pathway relationships and external hub-miRNA expression-profile evaluation
- External dataset evaluation: Yes
- Data modalities: plasma vesicle preparation and characterization, small-RNA sequencing, external qRT-PCR, target prediction and pathway enrichment, network analysis and PCoA

## What This Study Adds

- A plasma vesicle-associated small-RNA expression resource for DCM with chronic heart failure.
- A reported 92-feature differential set with computational target and pathway hypotheses.
- External expression-assay assessment of 10 hub miRNAs, with a clear distinction from the discovery-stage miR-185-5p finding.

## Evidence Scope

### Supports

- DCM-HF-associated plasma exosomal miRNA expression differences in the studied samples.
- An article-reported 92-feature screen and computational miRNA-target/pathway prioritization.
- Small external qRT-PCR evaluation of a selected 10-miRNA panel.
- Discovery-stage inclusion of hsa-miR-185-5p with the Table 1 values reported above.

### Does Not Establish

- A prospectively validated early diagnostic test or prognostic model for DCM.
- Causation of human DCM by the differential miRNAs or their predicted targets.
- External qRT-PCR validation of miR-185-5p in this article.
- Direct biochemical binding for every predicted miRNA-mRNA interaction.
- Cardiac-cell origin or exclusive exosomal origin of every measured circulating RNA.
- An effective miRNA-directed treatment in humans.

### Limitations

- The discovery participant count is not reliably established from the reviewed text; no synthetic total is supplied.
- The final Results screen uses absolute logFC >0.5, while Fig. 3A prints >0.05. P-value and FDR statements are not assumed to establish the same feature-wise threshold.
- Methods 2.9 includes an abdominal-aortic-wall/mRNA extraction passage inconsistent with the surrounding plasma-exosomal-miRNA assay description; this is retained as a reporting limitation, not reinterpreted as a myocardial tissue experiment.
- External evaluation is small (10 cases and 6 controls), and multivariate separation is not prospective diagnostic validation.
- Some feature labels retain homolog/isomiR-style naming in the source; the complete feature set is not relabeled as uniquely verified canonical human mature miRNAs.

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## When This Study Is Useful to Cite

### CU1: Which studies profiled plasma exosomal miRNAs in DCM with chronic heart failure?

This study combines small-RNA discovery with external qRT-PCR follow-up in human DCM-HF and healthy samples.

Evidence: [KF1](#kf1), [KF5](#kf5)

### CU2: How were plasma vesicle preparations characterized in the DCM miRNA study?

ExoQuick preparations were assessed by morphology, size and CD63/CD81/Calnexin marker readouts; the evidence does not establish cardiac origin.

Evidence: [KF2](#kf2)

### CU3: What differential miRNA landscape was reported in DCM-HF plasma exosomes?

The article reports 92 screened features, 48 up and 44 down; its Results and figure-caption threshold wording differ.

Evidence: [KF3](#kf3)

### CU4: What computational target networks were associated with DCM exosomal miRNAs?

The reported 55-node/59-edge network and pathway analyses are hypothesis-generating predictions.

Evidence: [KF4](#kf4)

### CU5: Was a DCM exosomal miRNA panel assessed in an external group?

Ten hubs were tested by qRT-PCR in 10 cases and 6 controls, with group-profile differences reported.

Evidence: [KF5](#kf5)

### CU6: What human observational evidence motivated later miR-185-5p studies?

This paper lists miR-185-5p as a discovery/network candidate, but not as one of its 10 externally qRT-PCR-tested hubs.

Evidence: [KF6](#kf6)

<a id="citation-boundaries"></a>
## What This Study Should Not Be Cited to Claim

- A prospectively validated early diagnostic test or prognostic model for DCM.
- Causation of human DCM by the differential miRNAs or their predicted targets.
- External qRT-PCR validation of miR-185-5p in this article.
- Direct biochemical binding for every predicted miRNA-mRNA interaction.
- Cardiac-cell origin or exclusive exosomal origin of every measured circulating RNA.
- An effective miRNA-directed treatment in humans.

<a id="evidence-matrix"></a>
## Evidence Matrix

<a id="evidence-dcm-mirna-design"></a>
### Human discovery and external assay design

- Context: DCM-HF versus healthy plasma samples
- Finding: The study combined human DCM-HF plasma miRNA discovery with a separate external expression-assay comparison. Disease phenotype: DCM with chronic heart failure; Discovery assay: Small-RNA library sequencing on Illumina HiSeq2500; External qRT-PCR sample: 10 DCM patients; 6 healthy controls
- Evidence Level: Human observational molecular profiling
- Scope: Do not infer an unreported complete discovery sample size or prospective clinical utility.
- Source Locator: Methods 2.1, 2.8 and 2.9; Results 3.10; Fig. 6
- Evidence refs: [KF1](#kf1)

<a id="evidence-dcm-mirna-vesicles"></a>
### Vesicle preparation characterization

- Context: Isolated plasma fraction
- Finding: The isolated plasma preparations showed vesicle morphology, size and marker findings consistent with the reported exosomal preparation. Isolation: ExoQuick precipitation; Median particle diameter: Approximately 81 nm in the reported groups; Marker findings: CD63 and CD81 detected; Calnexin not detected
- Evidence Level: Experimental specimen characterization
- Scope: These readouts do not identify the cardiac source of each vesicle.
- Source Locator: Methods 2.3-2.6; Results 3.1; Fig. 1B-D
- Evidence refs: [KF2](#kf2)

<a id="evidence-dcm-mirna-screen"></a>
### Differential miRNA feature screen

- Context: Discovery expression comparison
- Finding: The Results identify 92 differential miRNA features after the stated fold-change and P-value screen. Detected miRNA features: 3,687; Final threshold as stated in Results: Absolute logFC >0.5 and P<0.05; Final differential features: 92; Upregulated / downregulated: 48 / 44
- Evidence Level: Exploratory association screen
- Scope: No unverified uniform FDR claim or clinical operating threshold.
- Source Locator: Results 3.2; Table 1; Figs. 2 and 3A
- Evidence refs: [KF3](#kf3)

<a id="evidence-dcm-mirna-network"></a>
### Predicted miRNA-target and pathway relationships

- Context: Computational analysis
- Finding: Target prediction and network analysis connected differential miRNA features to candidate regulatory and pathway contexts. miRNA-mRNA network: 55 nodes: 32 miRNAs and 23 hub genes; Network edges: 59; Enrichment examples: Circadian entrainment, oxytocin signaling and Hippo-related pathways
- Evidence Level: In-silico target/network inference
- Scope: Predicted edges are not direct binding or target-protein measurements.
- Source Locator: Methods 2.10-2.12; Results 3.3-3.9; Figs. 3-5
- Evidence refs: [KF4](#kf4)

<a id="evidence-dcm-mirna-qpcr"></a>
### External hub-miRNA assay

- Context: 10 DCM and 6 healthy individuals
- Finding: External qRT-PCR and multivariate expression comparisons assessed a 10-miRNA hub panel in a small independent population. External sample: 10 DCM patients and 6 healthy controls; Hub miRNAs tested: 10; Readouts: qRT-PCR, Euclidean expression distance and PCoA
- Evidence Level: External expression-assay evaluation
- Scope: A small assay cohort does not establish early diagnosis or prognosis.
- Source Locator: Methods 2.9, 2.13 and 2.14; Results 3.10; Fig. 6
- Evidence refs: [KF5](#kf5)

<a id="evidence-dcm-mirna-mir185"></a>
### Discovery-stage miR-185-5p signal

- Context: Table 1 and external-panel comparison
- Finding: miR-185-5p was a discovery-stage signal and predicted-network candidate, rather than a member of the reported external 10-miRNA panel. Table 1 hsa-miR-185-5p logFC: 1.04; Table 1 hsa-miR-185-5p P value: 0.0322; External 10-miRNA panel membership: Not included in the listed qRT-PCR panel
- Evidence Level: Discovery association and candidate prioritization
- Scope: Not external validation of this specific miRNA or proof of causality.
- Source Locator: Table 1; Results 3.9-3.10; Methods 2.9
- Evidence refs: [KF6](#kf6)

## Q&A

### What kind of DCM evidence does this paper provide?

Human case-control plasma miRNA expression profiling with an external assay phase; it is not a treatment trial or prospective prediction study.

Evidence: KF1

### How many differential miRNA features were reported?

The final Results screen reports 92 features, split into 48 upregulated and 44 downregulated, using absolute logFC >0.5 and P<0.05. Fig. 3A prints a different logFC threshold; this discrepancy is not silently reconciled.

Evidence: KF3

### Were the predicted pathways and miRNA targets experimentally established?

No. Target, enrichment and network analyses nominate relationships; the 55-node, 59-edge miRNA-mRNA network does not establish direct target binding or pathway causality.

Evidence: KF4

### What was evaluated in the external population?

Ten selected hub miRNAs were assessed by qRT-PCR in 10 DCM patients and 6 healthy controls. Expression-distance and PCoA analyses supported group differences, not clinical diagnostic utility.

Evidence: KF5

### Was miR-185-5p one of the externally tested hub miRNAs?

No. It appears in Table 1 with logFC 1.04 and P=0.0322 and in the predicted-network discussion, but is absent from the 10-miRNA external qRT-PCR list.

Evidence: KF6

### Can the results be treated as a measured whole-plasma or myocardial tissue signature?

No. The reported study concerns isolated plasma vesicle-associated RNA. It does not establish myocardial origin or interchangeability with whole-plasma RNA measurements.

Evidence: KF1, KF2

## Concepts & Entities

### Disease

dilated cardiomyopathy, chronic heart failure

### Specimen

plasma extracellular vesicles, exosomal miRNAs

### Methods

small-RNA sequencing, qRT-PCR, miRNA target prediction, PCoA

### Entities

miR-185-5p, CD63, CD81

### Evidence

case-control molecular profiling, external assay evaluation

## Related Research

- [Differential Expression Spectrum of circRNA in Plasma Exosomes in Dilated Cardiomyopathy With Heart Failure](https://drgezhang.com/papers/doi-10-1111-jcmm-70258.html) — Complementary DCM-HF plasma vesicle RNA profiling focused on circRNAs rather than miRNAs. Neither paper establishes that the two assays form a combined validated test or that their participants are non-overlapping. (DOI: 10.1111/jcmm.70258)
- [Targeted Delivery of Exosome-Derived miRNA-185-5p Inhibitor via Liposomes Alleviates Apoptosis and Cuproptosis in Dilated Cardiomyopathy](https://drgezhang.com/papers/doi-10-2147-ijn-s522157.html) — The later liposomal miR-185-5p inhibition article cites this expression study. The connection is observational candidate prioritization followed by separate preclinical intervention experiments, not proof of human therapeutic efficacy. (DOI: 10.2147/ijn.s522157)
- [Plasma Olink Proteomics Reveals Novel Biomarkers for Prediction and Diagnosis in Dilated Cardiomyopathy with Heart Failure](https://drgezhang.com/papers/olink-dcm.html) — Related DCM-HF biomarker research at the plasma-protein level; its plasma Olink measurements are not interchangeable with vesicle-associated miRNA profiling. (DOI: 10.1021/acs.jproteome.4c00522)

## Publication & Provenance

- DOI: https://doi.org/10.1111/jcmm.17789
- Doi Url: https://doi.org/10.1111/jcmm.17789
- Publisher: https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.17789
- PubMed: https://pubmed.ncbi.nlm.nih.gov/37243441/
- Pmc Url: https://pmc.ncbi.nlm.nih.gov/articles/PMC10339102/
- Review Basis: Published main text, tables and figure legends at the cited primary sources. No independent reanalysis of participant-level data; unresolved reporting differences are identified in the evidence scope.
- Data Availability: Methods 2.8 states that raw sequencing data were uploaded to GEO, but no specific accession was verified from the reviewed text. The data-availability section also offers data on request. No accession or direct dataset link is inferred.

## Evidence-page notice

Author-controlled evidence page for this publication. The evidence synthesis below is distinct from the published abstract and does not replace the version of record. Reported inconsistencies are qualified rather than silently corrected.

## Links

- DOI: https://doi.org/10.1111/jcmm.17789
- HTML page: https://drgezhang.com/papers/doi-10-1111-jcmm-17789.html
- Google Scholar query: https://scholar.google.com/scholar?q=%22Differential%20expression%20profiles%20of%20plasma%20exosomal%20microRNAs%20in%20dilated%20cardiomyopathy%20with%20chronic%20heart%20failure%22
- ORCID: https://orcid.org/0000-0002-3116-3246