The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
A novel mouse model of lipotoxic cardiomyopathy
Open accessAbstract
Inherited and acquired cardiomyopathies are associated with marked intracellular lipid accumulation in the heart. To test the hypothesis that mismatch between myocardial fatty acid uptake and utilization leads to the accumulation of cardiotoxic lipid species, and to establish a mouse model of metabolic cardiomyopathy, we generated transgenic mouse lines that overexpress long-chain acyl-CoA synthetase in the heart (MHC-ACS). This protein plays an important role in vectorial fatty acid transport across the plasma membrane. MHC-ACS mice demonstrate cardiac-restricted expression of the transgene and marked cardiac myocyte triglyceride accumulation. Lipid accumulation is associated with initial cardiac hypertrophy, followed by the development of left-ventricular dysfunction and premature death. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining and cytochrome c release in transgenic hearts suggest that cardiac myocyte death occurs, in part, by lipid-induced programmed cell death. Taken together, our data demonstrate that fatty acid uptake/utilization mismatch in the heart leads to accumulation of lipid species toxic to cardiac myocytes. This novel mouse model will provide insight into the role of perturbations in myocardial lipid metabolism in the pathogenesis of inherited and acquired forms of heart failure.
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Cites
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Cited by
Triglyceride accumulation protects against fatty acid-induced lipotoxicity
Listenberger, L. L., Han, X., Lewis, S. E., Cases, S., Farese, R. V., Ory, D. S., & Schaffer, J. E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0630588100 · Cited by 2,075
Self-citationDefective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase
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Molecular mechanisms of diabetic cardiomyopathy
Bugger, H., & Abel, E. D. (2014) · Diabetologia · doi:10.1007/s00125-014-3171-6 · Cited by 903
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Unger, R. H. (2002) · Annual Review of Medicine · doi:10.1146/annurev.med.53.082901.104057 · Cited by 875
Metadata
- Authors
- Chiu, H.-C., Kovacs, A., Ford, D. A., Hsu, F.-F., Garcia, R., Herrero, P., Saffitz, J. E., & Schaffer, J. E.
- Venue
- Journal of Clinical Investigation
- Published
- 2001-04-01
- Volume
- 107
- Issue
- 7
- Pages
- 813-822
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2117820310
- Cited by
- 760
- References
- 50
- FWCI
- 18.59
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Chiu, H.-C., Kovacs, A., Ford, D. A., Hsu, F.-F., Garcia, R., Herrero, P., Saffitz, J. E., & Schaffer, J. E. (2001). A novel mouse model of lipotoxic cardiomyopathy. Journal of Clinical Investigation. https://doi.org/10.1172/jci10947
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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