Transient Notch Activation Induces Long-Term Gene Expression Changes Leading to Sick Sinus Syndrome in Mice.

ABSTRACT:

Rationale

Notch signaling programs cardiac conduction during development, and in the adult ventricle, injury-induced Notch reactivation initiates global transcriptional and epigenetic changes.

Objective

To determine whether Notch reactivation may stably alter atrial ion channel gene expression and arrhythmia inducibility.

Methods and results

To model an injury response and determine the effects of Notch signaling on atrial electrophysiology, we transiently activate Notch signaling within adult myocardium using a doxycycline-inducible genetic system (inducible Notch intracellular domain [iNICD]). Significant heart rate slowing and frequent sinus pauses are observed in iNICD mice when compared with controls. iNICD mice have structurally normal atria and preserved sinus

SUBMITTER: Qiao Y 

PROVIDER: S-EPMC5565396 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature