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Expression of the beta (slow)-isoform of MHC in the adult mouse heart causes dominant-negative functional effects
1 Department of Medicine, Albert Einstein College of Medicine, Bronx 10461; 3 State University of New York, Health Science Center, Syracuse 13210; 2 Division of Molecular Cardiovascular Biology, Department of Pediatrics, Children's Hospital Research Foundation, Cincinnati, Ohio 45229; and 4...
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Published in: | American journal of physiology. Heart and circulatory physiology 2000-02, Vol.278 (2), p.H412-H419 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 1 Department of Medicine,
Albert Einstein College of Medicine, Bronx 10461;
3 State University of New
York, Health Science Center, Syracuse 13210; 2
Division of Molecular Cardiovascular Biology,
Department of Pediatrics, Children's Hospital Research Foundation,
Cincinnati, Ohio 45229; and
4 Department of Molecular,
Cellular and Developmental Biology, University of Colorado, Boulder,
Colorado 80309
- and -myosin heavy chain (MHC),
the two MHC isoforms expressed in the mammalian heart, differ
quantitatively in their enzymatic activities. The MHC composition of
the heart can change dramatically in response to numerous stimuli,
leading to the hypothesis that changes in cardiac function can be
caused by myosin isoform shifts. However, this hypothesis has remained
unproven because the stimuli used to generate these shifts are complex
and accompanied by many additional physiological changes, including
alterations in cardiac mass and geometry. Adult mouse ventricles
normally express only -MHC (the faster motor). To determine whether
genetic alteration of the MHC isoform composition in the adult mouse
heart would result in changes in cardiac chamber mass and
contractility, we established transgenic mouse lines that express a
Myc-tagged -MHC molecule (the slower motor) in adult ventricular
tissue, one of which expreses 12% of its myosin as the transgene.
There is no evidence of hypertrophy, induction of hypertrophic markers,
and no histopathology. Myofibrillar
Ca 2+ -activated ATPase activity is
decreased by 23%, and Langendorff preparations demonstrate a
significant 15% decrease in systolic function in transgenic hearts.
These results suggest that even small shifts in the myosin isoform
composition of the myocardium can result in physiologically significant
changes in cardiac contractility and could be relevant to
cardiovascular disease.
myosin heavy chain; contractility; transgenic |
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ISSN: | 0363-6135 1522-1539 |
DOI: | 10.1152/ajpheart.2000.278.2.H412 |