| Targeted cardiac overexpression of A20 improves left ventricular performance and reduces compensatory hypertrophy after myocardial infarction. | |
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MedLine Citation:
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PMID: 17389268 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: A20 was originally characterized as a tumor necrosis factor-inducible gene in human umbilical vein endothelial cells. As an inhibitor of nuclear factor-kappaB signaling, A20 protects against apoptosis, inflammation, and cardiac hypertrophy. In the present study, we tested the hypothesis that cardiac-specific overexpression of A20 could protect the heart from myocardial infarction. METHODS AND RESULTS: We investigated the role of constitutive human A20 expression in acute myocardial infarction using a transgenic model. Transgenic mice containing the human A20 gene under the control of the alpha-myosin heavy chain promoter were constructed. Myocardial infarction was produced by coronary ligation in A20 transgenic mice and control animals. The extent of infarction was then quantified by 2-dimensional and M-mode echocardiography and by molecular and pathological analyses of heart samples in infarct and remote heart regions 7 days after myocardial infarction. Constitutive overexpression of A20 in the murine heart resulted in attenuated infarct size and improved cardiac function 7 days after myocardial infarction. Significantly, we found a decrease in nuclear factor-kappaB signaling and apoptosis, as well as proinflammatory response, cardiac remodeling, and interstitial fibrosis, in noninfarct regions in the hearts of constitutive A20-expressing animals compared with control animals. CONCLUSIONS: Cardiac-specific overexpression of A20 improves cardiac function and inhibits cardiac remodeling, apoptosis, inflammation, and fibrosis after acute myocardial infarction. |
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Authors:
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Hong-Liang Li; Ming-Lei Zhuo; Dong Wang; Ai-Bing Wang; Hua Cai; Li-Hong Sun; Qinglin Yang; Yue Huang; Yu-Sheng Wei; Peter P Liu; De-Pei Liu; Chih-Chuan Liang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-03-26 |
Journal Detail:
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Title: Circulation Volume: 115 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2007 Apr |
Date Detail:
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Created Date: 2007-04-10 Completed Date: 2007-05-07 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
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Languages: eng Pagination: 1885-94 Citation Subset: AIM; IM |
Affiliation:
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National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, PR China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis Apoptosis Regulatory Proteins / biosynthesis, genetics Cytokines / blood Fibrosis Genes, Synthetic Heart Ventricles / physiopathology* Humans Hypertrophy, Left Ventricular / etiology, prevention & control* I-kappa B Kinase / analysis Inflammation / etiology Inflammation Mediators / analysis Intracellular Signaling Peptides and Proteins / genetics, physiology* Mice Mice, Transgenic Myocardial Infarction / pathology*, physiopathology, ultrasonography Myocytes, Cardiac / pathology NF-kappa B / antagonists & inhibitors*, physiology Natriuretic Peptides / analysis Neutrophils / pathology Nuclear Proteins / genetics, physiology* Promoter Regions, Genetic Recombinant Fusion Proteins / physiology Signal Transduction Single-Blind Method Tumor Necrosis Factor-alpha / physiology Ventricular Dysfunction, Left / etiology, prevention & control* Ventricular Myosins / genetics Ventricular Remodeling / physiology |
| Chemical | |
Reg. No./Substance:
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0/Apoptosis Regulatory Proteins; 0/Cytokines; 0/Inflammation Mediators; 0/Intracellular Signaling Peptides and Proteins; 0/NF-kappa B; 0/Natriuretic Peptides; 0/Nuclear Proteins; 0/Recombinant Fusion Proteins; 0/Tumor Necrosis Factor-alpha; EC 2.7.11.10/I-kappa B Kinase; EC 3.6.1.-/Ventricular Myosins; EC 6.3.2.19/TNFAIP3 protein, human |
| Comments/Corrections | |
Comment In:
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Circulation. 2007 Apr 10;115(14):1827-9
[PMID:
17420361
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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