Targeting Cardiomyocyte PCNA and POLD1 Prevents Pathologic Myocardial Hypertrophy.

ABSTRACT:

Background

Activation of cell cycle regulatory pathways has been detected during pathological cardiomyocyte growth. However, it has remained unclear whether DNA synthesis pathways play a direct role in cardiomyocyte hypertrophy. We previously discovered in a mouse model of hypertrophic cardiomyopathy that there was increased DNA synthesis, which led to cardiomyocyte endoreplication and replication stress-induced DNA damage. We hypothesized that targeting cardiomyocyte endoreplication pathways could reduce pathological myocardial hypertrophy.

Methods

We utilized murine models of hypertrophic cardiomyopathy secondary to mutations in cardiac Mybpc3 (myosin-binding protein C3)^-/- or Myh6 (myosin heavy chain 6)^R404Q and transverse aortic constriction as a mo

SUBMITTER: Pal S 

PROVIDER: S-EPMC12509454 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature