Mitogen-activated protein kinase inhibitor regulation of heart function and fibrosis in cardiomyopathy caused by lamin A/C gene mutation

Abstract

Mutations in the lamin A/C gene (LMNA) encoding A-type nuclear lamins cause dilated cardiomyopathy. We have uncovered a novel connection between these mutations and hyperactivation of the extracellular signal-regulated kinase 1/2 and c-jun N-terminal kinase branches of the mitogen-activated protein kinase signaling pathway in a mouse model of the disease. This discovery has identified targets that can be inhibited by drugs that improve heart function and prevent fibrosis.