Omics · study · 2026
Humanin and MOTS-c Attenuate Atrial Fibrillation by Suppressing Fibrosis and Mitochondrial Dysfunction in murine models
Listed in NCBI GEO
BACKGROUND: Atrial fibrillation (AF) is the most common clinical arrhythmia associated with mitochondrial dysfunction, oxidative stress, and atrial fibrosis.
Description
Mitochondrial-derived peptides (MDPs) including humanin (HN) and MOTS-c, demonstrated potent cytoprotective effects, but their role in AF remains elusive. METHODS: Public GEO database, immunohistochemistry and immunofluorescence were applied to determine their expressions in atrial tissues.
Plasma peptide levels were measured in a clinical cohort. Murine AF models and primary rat cardiomyocytes and fibroblasts models were established by administration of angiotensin II (Ang II) and treated with (Gly14)-Humanin (HNG, an HN analogue) or MOTS-c. RESULTS: Both HN and MOTS-c gene expressions were significantly downregulated in human AF atrial tissue and negatively correlated with the extent of fibrosis.
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Plasma MOTS-c level decreased in AF patients and showed an inverse correlation with NT-proBNP. In vivo, administration of HNG or MOTS-c significantly reduced AF inducibility, attenuated atrial fibrosis and hypertrophy induced by Ang II. Furthermore, HNG or MOTS-c treatment improved mitochondrial ultrastructure, as well as downregulated the expressions of mitochondrial fission proteins (Drp1 and Fis1) and pro-inflammatory cytokines (IL-1β and IL-6) of atrial tissue in murine AF models.
In primary cardiomyocytes, both peptides mitigated Ang II-induced oxidative stress. In addition, they directly inhibited Ang II-induced fibroblast activation, proliferation, and migration in vitro. Further RNA sequencing results suggested that HNG mainly affects cell adhesion pathways and MOTS-c acts on metabolic process of cardiac fibroblasts.
CONCLUSIONS: The downregulation of HN and MOTS-c in human AF is associated with AF severity. Administration of HNG or MOTS-c effectively suppressing atrial fibrosis and mitochondrial dysfunction and prevents AF in murine models. Therefore, mitochondrial-derived peptides represent as the underappreciated contributor to AF therapy and potential biomarkers.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE322nnn/GSE322635 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE322635 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1430789 ncbi.nlm.nih.gov/bioproject/PRJNA1430789 ↗
project · from NCBI GEO
- PubMed 42193373 pubmed.ncbi.nlm.nih.gov/42193373 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Rattus norvegicus
- From keywords
- Life Sciences
- Inferred from text
- Heart 65% · RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE322635 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[anatomy].local:anatomy:heart | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[organism].NCBITaxon:10116 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |