Heart failure & cardiomyopathiesMechanistic study
Metformin inhibits proliferation of residing fibroadipogenic progenitor cells from failing human hearts
- in vivo positron emission tomography (PET) imaging and in vitro single-cell study
Authors' conclusion
Myocardial metformin uptake in HFrEF is marginal and confined to less viable and fibrotic regions. Cardiac FAPs are resident in human HFrEF myocardium and exhibit fibrogenic potential. Metformin inhibits FAP activation and proliferation at clinically relevant concentrations. These findings suggest that metformin may attenuate adverse left ventricular remodelling by targeting cardiac FAPs.
Study context
- Population
- Patients with heart failure with reduced ejection fraction (HFrEF)HFrEF patients, PET imaging seven · HFrEF patients, explanted left ventricles four · control human hearts four
- Comparison
- HFrEF patients vs control human hearts
- HFrEF patientsn = four
- control human heartsn = four
Main finding
As reported in the abstract
- best described by reversible two-tissue-compartment kinetics
Further findings
Global myocardial metformin net influx rate
- net influx rate
- 0.012 ± 0.007 ml ml-1 min-2
Myocardium-to-blood ratio · after 90 min
- myocardium-to-blood ratio
- 1.24 (95% confidence intervals: 1.03-1.44; P < .001)
Regional myocardial metformin net influx vs myocardial viability
- inverse correlation
- r = −0.65, P = .04
Cardiac FAPs by scRNA-seq
- cardiac FAPs expressing CD34 and PDGFRA, transformed into extracellular matrix-forming myogenic cells upon activation
FAP proliferation with metformin (0.1 mM)
- inhibition of FAP proliferation
- 25%
Original publication
Summarised from the published abstract; every number is checked against it