Heart failure & cardiomyopathies
CRLF1 Secreted by Cardiac Fibroblasts Promotes Human Hypertrophic Cardiomyopathy
Authors' conclusion
Our findings uncover a common, nongenetic paracrine mechanism underlying HCM pathogenesis and establish CRLF1 as a promising universal therapeutic target for this heterogeneous disease.
Study context
- Population
- Patients with obstructive hypertrophic cardiomyopathy (HCM) undergoing surgical myectomy (hypertrophied interventricular septum tissue); Myh6 R404Q/+ mouse model
- Participants
- 269 patients
Methodological detailscross-species validation, single-cell RNA sequencing, gain- and loss-of-function studies
- Cross-species validation
- Single-cell RNA sequencing
- Gain- and loss-of-function studies
Main finding
As reported in the abstract
- CRLF1, mainly secreted by activated cardiac fibroblasts, a key paracrine factor driving cardiomyocyte hypertrophy across genetically heterogeneous HCM
- CRLF1 levels significantly elevated in hypertrophied myocardium and circulation
- CRLF1 activated LIFR-JAK1/2-STAT3 signalling to promote hypertrophy in murine and human HCM models
- Fibroblast Crlf1 ablation or pharmacological inhibition of its downstream pathway markedly attenuated disease phenotypes
Original publication
CRLF1 Secreted by Cardiac Fibroblasts Promotes Human Hypertrophic Cardiomyopathy. Circulation. Published 16 March 2026. doi:10.
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