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

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 ERK and JNK signaling before the onset of cardiomyopathy in Lmna(H222P/H222P) mice prevented the development of left ventricle dilatation and decreased cardiac ejection fraction at a time when they occurred in untreated mice.