Cardiac Gene Therapy With Phosphodiesterase 2A Limits Remodeling and Arrhythmias in Mouse Models of Heart Failure.

ABSTRACT:

Background

PDE2 (phosphodiesterase 2) is upregulated in human heart failure. Cardiac PDE2-transgenic mice are protected against contractile dysfunction and arrhythmias in heart failure but whether an acute elevation of PDE2 could be of therapeutic value remains elusive. This hypothesis was tested using cardiac PDE2 gene transfer in preclinical models of heart failure.

Methods and results

C57BL/6 male mice were injected with serotype 9 adeno-associated viruses encoding for PDE2A. This led to a ≈10-fold rise of PDE2A protein levels that affected neither cardiac structure nor function in healthy mice. Two weeks after inoculation with serotype 9 adeno-associated viruses, mice were implanted with minipumps delivering either NaCl, isoproterenol (60 mg/kg per day), or isoproterenol

SUBMITTER: Kamel R 

PROVIDER: S-EPMC12074716 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature