Cardiomyocyte-specific PCSK9 deficiency compromises mitochondrial bioenergetics and heart function.

ABSTRACT:

Aims

Pro-protein convertase subtilisin-kexin type 9 (PCSK9), which is expressed mainly in the liver and at low levels in the heart, regulates cholesterol levels by directing low-density lipoprotein receptors to degradation. Studies to determine the role of PCSK9 in the heart are complicated by the close link between cardiac function and systemic lipid metabolism. Here, we sought to elucidate the function of PCSK9 specifically in the heart by generating and analysing mice with cardiomyocyte-specific Pcsk9 deficiency (CM-Pcsk9-/- mice) and by silencing Pcsk9 acutely in a cell culture model of adult cardiomyocyte-like cells.

Methods and results

Mice with cardiomyocyte-specific deletion of Pcsk9 had reduced contractile capacity, impaired cardiac function, and left ventricular di

SUBMITTER: Laudette M 

PROVIDER: S-EPMC10318396 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature