Heart failure & cardiomyopathies
Histamine N-methyltransferase upregulation, cardiac hypertrophy, and heart failure
Authors' conclusion
HNMT exacerbates pathological hypertrophy and HF through SAM/FZD2/CaMKII axis. Amodiaquine, the inhibitor of HNMT, shows therapeutic potential against HF. Urinary N-methylhistamine emerges as a non-invasive HF biomarker.
Study context
- Population
- Mice with transverse aortic constriction (TAC)-induced heart failure (HF); HF patients and controls
- Participants
- 53 vs 55
- Comparison
- HF vs Control
- HFn = 53
- Controln = 55reference
Methodological detailscardiomyocyte-specific Hnmt-knockout and Hnmt-overexpression mice, TAC model, human cohort
- Cardiomyocyte-specific Hnmt-knockout and Hnmt-overexpression mice
- TAC model
- Human cohort
Main finding
As reported in the abstract
- Histamine N-methyltransferase (HNMT) up-regulated in cardiac tissue from HF patients, TAC mice and phenylephrine (PE)-treated neonatal mouse cardiomyocytes (NMCMs)
- Urinary N-methylhistamine elevated in HF patients, positively correlated with HF severity
- Cardiomyocyte-specific Hnmt deletion mitigated hypertrophy and HF induced by TAC or angiotensin II
- HNMT inhibition with amodiaquine ameliorated TAC-induced cardiac dysfunction
- Hnmt overexpression impaired cardiac function
- HNMT reduced S-adenosylmethionine (SAM), impaired EZH2, decreased H3K27me3 at Fzd2 promoter; FZD2 up-regulation activated WNT/CaMKII pathway, promoting HF
Original publication
Histamine N-methyltransferase upregulation, cardiac hypertrophy, and heart failure. Eur Heart J. Published 22 January 2026. doi:10.
Summarised from the published abstract; every number is checked against it