期刊
NEUROMUSCULAR DISORDERS
卷 26, 期 8, 页码 490-499出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.nmd.2016.05.010
关键词
A-type lamin; L-CMD; Dilated cardiomyopathy; Mechanical stress; Chronic exercise
资金
- Institut National de la Sante et de la Recherche Medicale
- Association Francaise contre les Myopathies (AFM)
- Sorbonne Universites-Universite Pierre et Marie Curie Paris 06, the Centre National de la Recherche Scientifique
LMNA gene encodes lamin A/C, ubiquitous proteins of the nuclear envelope. They play crucial role in maintaining nuclear shape and stiffness. When mutated, they essentially lead to dilated cardiomyopathy with conduction defects, associated or not with muscular diseases. Excessive mechanical stress sensitivity has been involved in the pathophysiology. We have previously reported the phenotype of Lmna(delK32) mice, reproducing a mutation found in LMNA-related congenital muscular dystrophy patients. Heterozygous Lmna(delK321+) (Het) mice develop a progressive dilated cardiomyopathy leading to death between 35 and 70 weeks of age. To investigate the sensitivity of the skeletal muscles and myocardium to chronic exercise-induced stress, Het and wild-type (Wt) mice were subjected to strenuous running treadmill exercise for 5 weeks. Before exercise, the cardiac function of Het mice was similar to Wt-littermates. After the exercise-period, Het mice showed cardiac dysfunction and dilation without visible changes in cardiac morphology, molecular remodelling or nuclear structure compared to Wt exercised and Het sedentary mice. Contrary to myocardium, skeletal muscle ex vivo contractile function remained unaffected in Het exercised mice. In conclusion, the expression of the Lmna(delK2) mutation increased the susceptibility of the myocardium to cardiac stress and led to an earlier onset of the cardiac phenotype in Het mice. (C) 2016 Elsevier B.V. All rights reserved.
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