title: 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.
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Antoine
authors.initials: A
authors.lastname: Muchir
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Worman
mesh_terms: D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics*; D005355:Fibrosis; D006321:Heart / Q000503:physiopathology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D034904:Lamin Type A / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009206:Myocardium / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A; D047428:Protein Kinase Inhibitors; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases