title: In vivo cardiac role of migfilin during experimental pressure overload.
abstract: OBJECTIVE
  Increased myocardial wall strain triggers the cardiac hypertrophic response by increasing cardiomyocyte size, reprogramming gene expression, and enhancing contractile protein synthesis. The LIM protein, migfilin, is a cytoskeleton-associated protein that was found to translocate in vitro into the nucleus in a Ca(2+)-dependent manner, where it co-activates the pivotal cardiac transcription factor Csx/Nkx2.5. However, the in vivo role of migfilin in cardiac function and stress response is unclear.
  
  
  RESULTS
  To define the role of migfilin in cardiac hypertrophy, we induced hypertension by transverse aortic constriction (TAC) and compared cardiac morphology and function of migfilin knockout (KO) with wild-type (WT) hearts. Heart size and myocardial contractility were comparable in untreated migfilin KO and WT hearts, but migfilin-null hearts presented a reduced extent of hypertrophic remodelling in response to chronic hypertensile stress. Migfilin KO mice maintained their cardiac function for a longer time period compared with WT mice, which presented extensive fibrosis and death due to heart failure. Migfilin translocated into the nucleus of TAC-treated cardiomyocytes, and migfilin KO hearts showed reduced Akt activation during the early response to pressure overload.
  
  
  CONCLUSIONS
  Our findings indicate an important role of migfilin in the regulation of cardiac hypertrophy upon experimental TAC.
authors: Department of Internal Medicine III/Cardiology, Innsbruck Medical University, Anichstr. 35, Innsbruck A-6020, Austria.
authors: Bernhard Johannes
authors: BJ
authors: Haubner
authors: Department of Molecular Medicine, Max-Planck-Institute of Biochemistry, Martinsried, Germany.
authors: Daniel
authors: D
authors: Moik
authors: Department of Internal Medicine III/Cardiology, Innsbruck Medical University, Anichstr. 35, Innsbruck A-6020, Austria.
authors: Thomas
authors: T
authors: Schuetz
authors: Department of Internal Medicine III/Cardiology, Innsbruck Medical University, Anichstr. 35, Innsbruck A-6020, Austria.
authors: Martin F
authors: MF
authors: Reiner
authors: Department of Internal Medicine III/Cardiology, Innsbruck Medical University, Anichstr. 35, Innsbruck A-6020, Austria.
authors: Jakob G
authors: JG
authors: Voelkl
authors: Department of Internal Medicine III/Cardiology, Innsbruck Medical University, Anichstr. 35, Innsbruck A-6020, Austria.
authors: Katrin
authors: K
authors: Streil
authors: Department of Internal Medicine III/Cardiology, Innsbruck Medical University, Anichstr. 35, Innsbruck A-6020, Austria.
authors: Kerstin
authors: K
authors: Bader
authors: Department of Internal Medicine III/Cardiology, Innsbruck Medical University, Anichstr. 35, Innsbruck A-6020, Austria.
authors: Lei
authors: L
authors: Zhao
authors: Department of Internal Medicine III/Cardiology, Innsbruck Medical University, Anichstr. 35, Innsbruck A-6020, Austria.
authors: Claudia
authors: C
authors: Scheu
authors: Department of Internal Medicine III/Cardiology, Innsbruck Medical University, Anichstr. 35, Innsbruck A-6020, Austria.
authors: Johannes
authors: J
authors: Mair
authors: Department of Internal Medicine III/Cardiology, Innsbruck Medical University, Anichstr. 35, Innsbruck A-6020, Austria.
authors: Otmar
authors: O
authors: Pachinger
authors: Department of Internal Medicine III/Cardiology, Innsbruck Medical University, Anichstr. 35, Innsbruck A-6020, Austria bernhard.metzler@uki.at.
authors: Bernhard
authors: B
authors: Metzler
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005355:Fibrosis; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D006973:Hypertension / Q000150:complications* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D020257:Ventricular Remodeling
chemical_list: D015815:Cell Adhesion Molecules; C489422:Fblim1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Cardiac function; Cardiac hypertrophy; Migfilin; Myocardial remodelling; Pressure overload