Heart failure & cardiomyopathiesResearch article
Sex-Dependent Fibroblast Signatures in Heart Failure: Toward Stratified Anti-Fibro-Inflammatory Therapies
- Cardiac fibroblasts isolated from endomyocardial biopsies analyzed in vitro and by single-cell RNA sequencing
- age-matched
Authors' conclusion
Our findings suggest sexual dimorphism in cardiac fibroblast biology with potentially distinct mechanisms. Sex may influence fibroblast activation states that shift in heart failure, underscoring the relevance of considering sex in anti-fibrotic strategies and the use of fibroblasts for individualized disease profiling.
Study context
- Population
- Heart failure patients with LVEF<50% and age-matched patients with LVEF≥50%each group: n=6, 3 men vs. 3 women · LVEF<50% 6 · LVEF≥50% 6
- Participants
- 6 vs 6
- Comparison
- LVEF<50% vs LVEF≥50%
- LVEF<50%n = 6
- LVEF≥50%n = 6
Main finding
As reported in the abstract
Metabolic activity
- Higher activity in female compared to male fibroblasts in the LVEF<50% patient group; the reverse in the LVEF≥50% group
Further findings
Collagen deposition and α-SMA expression (LVEF<50%)
- Female fibroblasts deposited more collagen despite lower α-SMA expression
Morphology
- Female cells more polarized and asymmetric than male cells in LVEF<50%; less pronounced in the LVEF≥50% patient group
Transcriptomic activation programs
- Male fibroblasts: broad enrichment of TGF-β-driven extracellular matrix remodeling pathways
- Female fibroblasts: IL-1-associated remodeling and selective activation of distinct fibroblast subsets
Original publication
Sex-Dependent Fibroblast Signatures in Heart Failure: Toward Stratified Anti-Fibro-Inflammatory Therapies. ESC Heart Fail. Published 28 May 2026. doi:10.1093/eschf/xvag147
Summarised from the published abstract; every number is checked against it