Mechanistic Insights of the LEMD2 p.L13R Mutation and Its Role in Cardiomyopathy.
Ruping ChenSimone BuchmannAmos KrothAnahi Paula Arias-LozaMichael KohlhaasNicole WagnerGianna GrünerAlexander G NickelAlexandra CirnuTatjana WilliamsChristoph MaackSüleyman ErgünStefan FrantzBrenda GerullPublished in: Circulation research (2023)
We show for the first time that the Lemd2 p.L13R mutation in mice recapitulates human dilated cardiomyopathy with fibrosis and severe ventricular arrhythmias. Impaired nuclear envelope rupture repair capacity resulted in increased DNA damage and activation of the cGAS/STING/IFN pathway, promoting premature senescence. Hence, LEMD2 is a new player inthe disease group of laminopathies.
Keyphrases
- dna damage
- endothelial cells
- heart failure
- dna repair
- oxidative stress
- immune response
- dendritic cells
- left ventricular
- induced pluripotent stem cells
- early onset
- high fat diet induced
- type diabetes
- pluripotent stem cells
- metabolic syndrome
- insulin resistance
- stress induced
- atrial fibrillation
- drug induced
- liver fibrosis