| Coexistence of cardiac troponin T variants reduces heart efficiency. | |
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MedLine Citation:
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PMID: 20418479 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Corresponding to the synchronized contraction of the myocardium and rhythmic pumping function of the heart, a single form of cardiac troponin T (cTnT) is present in the adult cardiac muscle of humans and most other vertebrate species. Alternative splicing variants of cTnT are found in failing human hearts and animal dilated cardiomyopathies. Biochemical analyses have shown that these cTnT variants are functional and produce shifted myofilament Ca(2+) sensitivity. We proposed a hypothesis that the coexistence of two or more functionally distinct TnT variants in the adult ventricular muscle that is normally activated as a syncytium may decrease heart function and cause cardiomyopathy (Huang et al., Am J Physiol Cell Physiol 294: C213-C222, 2008). In the present study, we studied transgenic mouse hearts expressing one or two cTnT variants in addition to normal adult cTnT to investigate whether desynchronized myofilament activation decreases ventricular efficiency. The function of ex vivo working hearts was examined in the absence of systemic neurohumoral influence. The results showed that the transgenic mouse hearts produced lower maximum left ventricular pressure, slower contractile and relaxation velocities, and decreased stroke volume compared with wild-type controls. Ventricular pumping efficiency, calculated by the ejection integral versus total systolic integral and cardiac work versus oxygen consumption, was significantly lower in transgenic mouse hearts and corresponded to the number of cTnT variants present. The results indicated a pathogenic mechanism in which the coexistence of functionally different cTnT variants in cardiac muscle reduces myocardial efficiency due to desynchronized thin filament activation. |
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Authors:
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Han-Zhong Feng; J-P Jin |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-04-23 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 299 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-06-17 Completed Date: 2010-07-06 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H97-H105 Citation Subset: IM |
Affiliation:
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Department of Physiology, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alternative Splicing Animals Exons Mice Mice, Transgenic Microfilaments / metabolism* Myocardial Contraction* Myocardium / metabolism* Oxygen Consumption Protein Isoforms Stroke Volume Time Factors Troponin T / genetics, metabolism* Ventricular Function, Left* Ventricular Pressure |
| Grant Support | |
ID/Acronym/Agency:
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AR-048816/AR/NIAMS NIH HHS; HL-078773/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Protein Isoforms; 0/Troponin T |
| Comments/Corrections | |
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