Ranolazine rescues the heart failure phenotype of PLN-deficient human pluripotent stem cell-derived cardiomyocytes.

ABSTRACT: Phospholamban (PLN) is a key regulator that controls the function of the sarcoplasmic reticulum (SR) and is required for the regulation of cardiac contractile function. Although PLN-deficient mice demonstrated improved cardiac function, PLN loss in humans can result in dilated cardiomyopathy (DCM) or heart failure (HF). The CRISPR-Cas9 technology was used to create a PLN knockout human induced pluripotent stem cell (hiPSC) line in this study. PLN deletion hiPSCs-CMs had enhanced contractility at day 30, but proceeded to a cardiac failure phenotype at day 60, with decreased contractility, mitochondrial damage, increased ROS production, cellular energy metabolism imbalance, and poor Ca²⁺ handling. Furthermore, adding ranolazine to PLN knockout hiPSCs-CMs at day 60 can partially re

SUBMITTER: Jiang Y 

PROVIDER: S-EPMC9023809 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature