1. In vivo cardiac role of migfilin during experimental pressure overload.
- Author
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Haubner BJ, Moik D, Schuetz T, Reiner MF, Voelkl JG, Streil K, Bader K, Zhao L, Scheu C, Mair J, Pachinger O, and Metzler B
- Subjects
- Active Transport, Cell Nucleus, Animals, Cell Adhesion Molecules deficiency, Cell Adhesion Molecules genetics, Disease Models, Animal, Enzyme Activation, Extracellular Signal-Regulated MAP Kinases metabolism, Fibrosis, Heart Failure genetics, Heart Failure metabolism, Heart Failure physiopathology, Hypertension physiopathology, Hypertrophy, Left Ventricular genetics, Hypertrophy, Left Ventricular pathology, Hypertrophy, Left Ventricular physiopathology, Hypertrophy, Left Ventricular prevention & control, Male, Mice, Inbred C57BL, Mice, Knockout, Myocytes, Cardiac pathology, Proto-Oncogene Proteins c-akt metabolism, Signal Transduction, Time Factors, Cell Adhesion Molecules metabolism, Hypertension complications, Hypertrophy, Left Ventricular metabolism, Myocytes, Cardiac metabolism, Ventricular Remodeling
- Abstract
Aims: 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., Methods and 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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)
- Published
- 2015
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