Heart failure & cardiomyopathies
Restoration of Cardiac Myosin Light Chain Kinase Ameliorates Systolic Dysfunction by Reducing Superrelaxed Myosin
Authors' conclusion
cMLCK dysregulation contributes to the development of cardiac systolic dysfunction in humans.
Study context
- Population
- Knock-in mice and human iPSC-derived cardiomyocytes carrying a DCM-associated MYLK3 frameshift mutation (c.1951–1G>T; p.P639Vfs*15); human myocardium from advanced HF
- Comparison
- cMLCK restoration vs MYLK3 frameshift mutation
- Outcome
- cMLCK expression, MLC2v phosphorylation, superrelaxation/disordered relaxation ratio and systolic/contractile function
Methodological detailsknock-in mice, human iPSC-derived cardiomyocytes, small-molecule activator
- Knock-in mice
- Human iPSC-derived cardiomyocytes
- Small-molecule activator
Main finding
As reported in the abstract
MYLK3+/fs hiPSC-CMs: reduced cMLCK expression and contractile dysfunction with increased superrelaxation/disordered relaxation ratio
cMLCK expression reduced by 50%
Parts of this Brief are withheld: the automatic checks could not confirm them against the abstract.
Original publication
Restoration of Cardiac Myosin Light Chain Kinase Ameliorates Systolic Dysfunction by Reducing Superrelaxed Myosin. Circulation. Published 2 May 2023. doi:10.
Summarised from the published abstract; every number is checked against it