Nature Review Maps 4 Key Fibroblast Drivers of HFpEF Fibrosis

1 articles · Updated · BIOENGINEER.ORG · Aug 18

A new Nature Reviews Cardiology paper argues myocardial fibrosis in HFpEF is driven by multiple cardiac fibroblast states, not a single scar-forming myofibroblast population.
Single-cell RNA sequencing and spatial transcriptomics showed fibroblasts occupy distinct niches near vessels, cardiomyocytes and immune cells, helping spread profibrotic programs through the heart.
Nitrosative stress, disrupted lipid metabolism, hypertension-linked mechanical stress and immune-vascular signaling emerged as major pathways pushing fibroblasts toward persistent matrix production, inflammation and arrhythmia risk.
The review says obesity, diabetes, kidney disease, ageing and signals from adipose tissue, gut, liver and bone marrow may help explain why HFpEF varies widely between patients.
That heterogeneity points to precision antifibrotic therapy—targeting harmful fibroblast programs while preserving normal repair—with biomarkers and imaging needed to identify patients most likely to benefit.