Reversible Fibroblast Trajectories Regulated by MR Underlie Diastolic Dysfunction - PubMed
5 hours ago
- #MR Antagonists
- #Heart Failure
- #Fibroblast Trajectories
- HFpEF is a significant health issue with diverse pathophysiology linked to comorbidities like kidney disease or obesity, and limited treatment options.
- MR antagonists show beneficial effects in HFpEF, but underlying mechanisms are incompletely understood.
- Mice treated with aldosterone and high-salt diet developed a reversible cardiorenal HFpEF-like phenotype with diastolic dysfunction.
- Single-nucleus RNA sequencing revealed gene expression changes in cardiomyocytes, endothelial cells, and fibroblasts after aldosterone treatment.
- Aldosterone induced a fibroblast subpopulation shift distinct from myofibroblasts seen in heart failure with reduced ejection fraction.
- Comparison with high-fat diet-induced HFpEF showed overlapping upregulation of MR target genes in both models.
- Fibroblast-specific MR deletion prevented diastolic dysfunction in HFpEF, differing from its role in heart failure with reduced ejection fraction.
- MR activation is a common feature in cardiorenal and cardiometabolic disease models, and fibroblast MR inhibition may underlie MR antagonist benefits in HFpEF.