<i>HRAS</i>-Mutant Cardiomyocyte Model of Multifocal Atrial Tachycardia.

ABSTRACT:

Background

Germline HRAS gain-of-function pathogenic variants cause Costello syndrome (CS). During early childhood, 50% of patients develop multifocal atrial tachycardia, a treatment-resistant tachyarrhythmia of unknown pathogenesis. This study investigated how overactive HRAS activity triggers arrhythmogenesis in atrial-like cardiomyocytes (ACMs) derived from human-induced pluripotent stem cells bearing CS-associated HRAS variants.

Methods

HRAS Gly12 mutations were introduced into a human-induced pluripotent stem cells-ACM reporter line. Human-induced pluripotent stem cells were generated from patients with CS exhibiting tachyarrhythmia. Calcium transients and action potentials were assessed in induced pluripotent stem cell-derived ACMs. Automated patch

SUBMITTER: Rodriguez NA 

PROVIDER: S-EPMC11021157 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature