LMNA-related dilated cardiomyopathy

Expanding the phenotype of LMNA mutations in dilated cardiomyopathy and functional consequences of these mutations.

AIMS Mutations in the lamin A/C gene (LMNA) have been reported to be involved in dilated cardiomyopathy (DCM) associated with conduction system disease and/or skeletal myopathy. The aim of this study was to perform a mutational analysis of LMNA in a large white population of patients affected by dilated cardiomyopathy with or without associated symptoms. METHODS We performed screening of the ...

Heart Failure Mitogen-Activated Protein Kinase Inhibitors Improve Heart Function and Prevent Fibrosis in Cardiomyopathy Caused by Mutation in Lamin A/C Gene

Background—Mutations in the lamin A/C gene, LMNA, can cause dilated cardiomyopathy. We have shown abnormal activation of the extracellular signal-regulated kinase (ERK) and the c-jun N-terminal kinase (JNK) branches of the mitogen-activated protein kinase signaling cascade in hearts from Lmna mice that develop dilated cardiomyopathy. We recently showed that partial inhibition of ERK and JNK sig...

Mitogen-activated protein kinase inhibitors improve heart function and prevent fibrosis in cardiomyopathy caused by mutation in lamin A/C gene.

BACKGROUND Mutations in the lamin A/C gene, LMNA, can cause dilated cardiomyopathy. We have shown abnormal activation of the extracellular signal-regulated kinase (ERK) and the c-jun N-terminal kinase (JNK) branches of the mitogen-activated protein kinase signaling cascade in hearts from Lmna(H222P/H222P) mice that develop dilated cardiomyopathy. We recently showed that partial inhibition of ER...

Treatment with selumetinib preserves cardiac function and improves survival in cardiomyopathy caused by mutation in the lamin A/C gene.

AIMS Mutations in A-type nuclear lamins gene, LMNA, lead to a dilated cardiomyopathy. We have reported abnormal activation of the extracellular signal-regulated kinase1/2 (ERK1/2) signalling in hearts from Lmna(H222P/H222P) mice, which develop dilated cardiomyopathy. We therefore determined whether an inhibitor of ERK1/2 signalling that has been investigated in clinical trials for cancer has th...

MEK1/2 Inhibitors to Treat Dilated Cardiomyopathy Caused by LMNA Mutations