Abstract | BACKGROUND: METHODS AND RESULTS: We found that cardiac-specific PHD inactivation causes ultrastructural, histological, and functional changes reminiscent of ischemic cardiomyopathy over time. Moreover, long-term expression of a stabilized hypoxia-inducible factor alpha variant in cardiomyocytes also led to dilated cardiomyopathy. CONCLUSIONS: Sustained loss of PHD activity and subsequent hypoxia-inducible factor activation, as would occur in the setting of chronic ischemia, are sufficient to account for many of the changes in the hearts of individuals with chronic coronary artery disease.
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Authors | Javid Moslehi, Yoji Andrew Minamishima, Jianru Shi, Donna Neuberg, David M Charytan, Robert F Padera, Sabina Signoretti, Ronglih Liao, William G Kaelin Jr |
Journal | Circulation
(Circulation)
Vol. 122
Issue 10
Pg. 1004-16
(Sep 07 2010)
ISSN: 1524-4539 [Electronic] United States |
PMID | 20733101
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Basic Helix-Loop-Helix Transcription Factors
- Hif1a protein, mouse
- Hypoxia-Inducible Factor 1, alpha Subunit
- endothelial PAS domain-containing protein 1
- PHD3 protein, mouse
- Procollagen-Proline Dioxygenase
- Egln1 protein, mouse
- Hypoxia-Inducible Factor-Proline Dioxygenases
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Topics |
- Animals
- Basic Helix-Loop-Helix Transcription Factors
(metabolism)
- Cardiomyopathy, Dilated
(metabolism, physiopathology)
- Cell Hypoxia
(physiology)
- Heart Failure
(metabolism, physiopathology)
- Hypoxia-Inducible Factor 1, alpha Subunit
(metabolism)
- Hypoxia-Inducible Factor-Proline Dioxygenases
- Mice
- Mice, Inbred C57BL
- Mice, Mutant Strains
- Mitochondria
(metabolism)
- Myocardial Stunning
(metabolism, physiopathology)
- Myocardium
(metabolism)
- Myocytes, Cardiac
(cytology, enzymology)
- Neovascularization, Physiologic
(physiology)
- Phenotype
- Procollagen-Proline Dioxygenase
(genetics, metabolism)
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