Heart failure & cardiomyopathiesResearch article
Inhibition of adenosine kinase alleviates hypertrophic cardiomyopathy by ameliorating coronary microvascular dysfunction
- Mendelian randomization and colocalization analyses
- drug repurposing with molecular docking, dynamics simulations, and cellular thermal shift assay
- validated in hypertrophic cardiomyopathy (HCM) mice and endothelial cells (EC)
Authors' conclusion
Our study established ADK as a therapeutic target for HCM treatment. Targeting ADK is a promising strategy for ameliorating microvascular dysfunction in HCM. Drug repurposing findings suggest that dabigatran may confer benefits in HCM via ADK inhibition.
Study context
- Population
- HCM genome-wide association data (FinnGen; IEU OpenGWAS)FinnGen cases 1,376 · FinnGen controls 210,300 · IEU OpenGWAS cases 507 · IEU OpenGWAS controls 489,220
Main finding
As reported in the abstract
ADK as a causal gene for HCM
Mendelian randomization OR
1.10, 95%CI 1.02-1.19, P = .015
validation OR
1.28, 1.01-1.61, P = .039
colocalization PP.H4
82.0%
Further findings
Adenosine kinase (ADK) inhibition in HCM mice
- ADK inhibition attenuated cardiac hypertrophy, fibrosis, and microvascular dysfunction
ADK inhibition in ECs in vitro
- ADK inhibition rescued the impaired function of ECs induced by Ang II stimulation
Drug repurposing: dabigatran binding to ADK
- highest binding energy
- −9.3 kcal/mol
- confirmed using molecular dynamics simulations and cellular thermal shift assay
Dabigatran effects
- dabigatran improved EC function in vitro and, in HCM mice, ameliorated microvascular dysfunction and pathological cardiac remodelling
Original publication
Inhibition of adenosine kinase alleviates hypertrophic cardiomyopathy by ameliorating coronary microvascular dysfunction. ESC Heart Fail. Published 22 April 2026. doi:10.1093/eschf/xvag118
Summarised from the published abstract; every number is checked against it