MOTS-c · research summary

Humanin and MOTS-c Attenuate Atrial Fibrillation by Suppressing Fibrosis and Mitochondrial Dysfunction.

Biomedicines · 2026. Summary drawn from the study's full text. Each statement is followed by the exact sentence it comes from. This is a research summary, not medical advice.

Study type

Exploratory mechanistic study involving human tissue/plasma analysis, murine in vivo models, and primary cell cultures.
“As this study was designed as an exploratory mechanistic investigation, a single primary outcome measure was not predefined for sample size calculation.”

Subjects

Human AF and sinus rhythm patients, male C57BL/6J mice, and primary rat atrial cardiomyocytes and fibroblasts.
“Participants in both cohorts were consecutively enrolled (not randomly selected) as they presented for routine health examinations or cardiac surgery.”

Sample size

39 matched human pairs for plasma, 13 human tissue samples, 32 mice, and primary rat cells.
“Consequently, 39 matched pairs (n = 39 per group) were included in the final analysis.”

Duration

3 weeks for the murine AngII infusion and peptide treatment period.
“Mice were infused subcutaneously with saline or AngII (T8560, TargetMol, USA) at a dose of 3 mg/kg/d via osmotic mini-pumps (2004w, Shenzhen RWD Life Science Co., Ltd., Shenzhen, China) for 3 weeks as described previously [29].”

Reported findings

HN and MOTS-c are downregulated in human AF atrial tissue and inversely correlate with fibrosis extent.
“HN and MOTS-c were significantly downregulated in human AF atrial tissue, and their levels inversely correlated with fibrosis extent.”
HNG or MOTS-c treatment reduced AF inducibility and attenuated AngII-induced atrial fibrosis and hypertrophy in mice.
“In vivo, HNG or MOTS-c treatment reduced AF inducibility and attenuated AngII-induced atrial fibrosis and hypertrophy.”
Peptide treatment improved mitochondrial ultrastructure, reduced mitochondrial fission proteins, and lowered pro-inflammatory cytokines in mouse atria.
“Peptide treatment was associated with improved mitochondrial ultrastructure, reduced mitochondrial fission proteins (Drp1, Fis1), and lower pro-inflammatory cytokines (IL-1β, IL-6) in mouse atria.”

Limitations stated by the authors

Modest human sample sizes, use of a subacute AngII mouse model that does not fully recapitulate chronic AF, lack of peptide-only control groups, and unknown specific receptors/signaling pathways.
“First, the human sample sizes are modest (39 matched pairs for plasma, 13 for atrial tissue), and the spatial transcriptomics dataset included only two donors per group.”

Source: PubMed 42193373 · DOI 10.3390/biomedicines14051048 · all study summaries

Duration

3 weeks for the murine AngII infusion and peptide treatment period.

“Mice were infused subcutaneously with saline or AngII (T8560, TargetMol, USA) at a dose of 3 mg/kg/d via osmotic mini-pumps (2004w, Shenzhen RWD Life Science Co., Ltd., Shenzhen, China) for 3 weeks as described previously [29].”

Reported findings

HN and MOTS-c are downregulated in human AF atrial tissue and inversely correlate with fibrosis extent.

“HN and MOTS-c were significantly downregulated in human AF atrial tissue, and their levels inversely correlated with fibrosis extent.”

HNG or MOTS-c treatment reduced AF inducibility and attenuated AngII-induced atrial fibrosis and hypertrophy in mice.

“In vivo, HNG or MOTS-c treatment reduced AF inducibility and attenuated AngII-induced atrial fibrosis and hypertrophy.”

Peptide treatment improved mitochondrial ultrastructure, reduced mitochondrial fission proteins, and lowered pro-inflammatory cytokines in mouse atria.

“Peptide treatment was associated with improved mitochondrial ultrastructure, reduced mitochondrial fission proteins (Drp1, Fis1), and lower pro-inflammatory cytokines (IL-1β, IL-6) in mouse atria.”

Limitations stated by the authors

Modest human sample sizes, use of a subacute AngII mouse model that does not fully recapitulate chronic AF, lack of peptide-only control groups, and unknown specific receptors/signaling pathways.

“First, the human sample sizes are modest (39 matched pairs for plasma, 13 for atrial tissue), and the spatial transcriptomics dataset included only two donors per group.”