Deletion of the Lmna gene in fibroblasts causes senescence-associated dilated cardiomyopathy by activating the double-stranded DNA damage response and induction of senescence-associated secretory phenotype.

ABSTRACT:

Introduction

Mutations in the LMNA gene, encoding Lamin A/C (LMNA), are established causes of dilated cardiomyopathy (DCM). The phenotype is typically characterized by progressive cardiac conduction defects, arrhythmias, heart failure, and premature death. DCM is primarily considered a disease of cardiac myocytes. However, LMNA is also expressed in other cardiac cell types, including fibroblasts.

Aim

The purpose of the study was to determine the contribution of the fibroblasts to DCM caused by LMNA deficiency.

Methods and results

The Lmna gene was deleted by crossing the platelet-derived growth factor receptor α-Cre recombinase (Pdgfra-Cre) and floxed Lmna (Lmna ^F/F) mice. The LMNA protein was nearly absent in ~80% of the

SUBMITTER: Rouhi L 

PROVIDER: S-EPMC9311325 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature