In PLN-R14del mice, SR structure restoration, rather than calcium cycling, is the dominant effector of PLN-ASO treatment.

ABSTRACT:

Aims

Phospholamban (PLN) acts as an inhibitory regulator of calcium uptake in the sarco-/endoplasmic reticulum (SR) of cardiomyocytes. The pathogenic variant, PLN-R14del, leads to dilated and/or arrhythmogenic cardiomyopathy. Previous studies demonstrated that PLN-targeting antisense oligonucleotides (ASOs) can mitigate disease progression in mice. However, it remains unclear whether the protective effects of PLN-ASO therapy are due to improved calcium homeostasis or via reduction of abnormal PLN-SR clusters, a hallmark of this disease.

Methods and results

Homozygous PLN-R14del (R14Δ/Δ) mice were randomized to injections with various doses of PLN-ASO (3, 7, 15, or 25 mg/kg) or a scrambled control. Consistent with previous findings, R14Δ/Δ mice exhibited severe cardiac dysfun

SUBMITTER: Sun L 

PROVIDER: S-EPMC12560789 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature