Restoration of Cardiac Myosin Light Chain Kinase Ameliorates Systolic Dysfunction by Reducing Superrelaxed Myosin.

ABSTRACT:

Background

Cardiac-specific myosin light chain kinase (cMLCK), encoded by MYLK3, regulates cardiac contractility through phosphorylation of ventricular myosin regulatory light chain. However, the pathophysiological and therapeutic implications of cMLCK in human heart failure remain unclear. We aimed to investigate whether cMLCK dysregulation causes cardiac dysfunction and whether the restoration of cMLCK could be a novel myotropic therapy for systolic heart failure.

Methods

We generated the knock-in mice (Mylk3^+/fs and Mylk3^fs/fs) with a familial dilated cardiomyopathy-associated MYLK3 frameshift mutation (MYLK3^+/fs) that had been identified previously by us (c.1951-1G>T; p.P639Vfs*15) and the human induced

SUBMITTER: Hitsumoto T 

PROVIDER: S-EPMC10270284 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature