Gene Therapy With the N-Terminus of Junctophilin-2 Improves Heart Failure in Mice.

ABSTRACT:

Background

Transcriptional remodeling is known to contribute to heart failure (HF). Targeting stress-dependent gene expression mechanisms may represent a clinically relevant gene therapy option. We recently uncovered a salutary mechanism in the heart whereby JP2 (junctophilin-2), an essential component of the excitation-contraction coupling apparatus, is site-specifically cleaved and releases an N-terminal fragment (JP2NT [N-terminal fragment of JP2]) that translocates into the nucleus and functions as a transcriptional repressor of HF-related genes. This study aims to determine whether JP2NT can be leveraged by gene therapy techniques for attenuating HF progression in a preclinical pressure overload model.

Methods

We intraventricularly injected adeno-associated virus (AAV)

SUBMITTER: Wang J 

PROVIDER: S-EPMC9050933 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature