Abstract |
The early genetic pathway(s) triggering the pathogenesis of coronary artery disease (CAD) and myocardial infarction (MI) remain largely unknown. Here, we describe an autosomal dominant form of CAD/MI ( adCAD1) that is caused by the deletion of seven amino acids in transcription factor MEF2A. The deletion disrupts nuclear localization of MEF2A, reduces MEF2A-mediated transcription activation, and abolishes synergistic activation by MEF2A and by the transcription factor GATA-1 through a dominant-negative mechanism. The MEF2A protein demonstrates strong expression in the endothelium of coronary arteries. These results identify a pathogenic gene for a familial vascular disease with features of CAD and implicate the MEF2A signaling pathway in the pathogenesis of CAD/MI.
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Authors | Lejin Wang, Chun Fan, Sarah E Topol, Eric J Topol, Qing Wang |
Journal | Science (New York, N.Y.)
(Science)
Vol. 302
Issue 5650
Pg. 1578-81
(Nov 28 2003)
ISSN: 1095-9203 [Electronic] United States |
PMID | 14645853
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- DNA-Binding Proteins
- Erythroid-Specific DNA-Binding Factors
- GATA1 Transcription Factor
- GATA1 protein, human
- Gata1 protein, rat
- Genetic Markers
- MADS Domain Proteins
- MEF2 Transcription Factors
- MEF2A protein, human
- Myogenic Regulatory Factors
- Transcription Factors
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Topics |
- Aged
- Amino Acid Sequence
- Animals
- Arteries
(metabolism)
- Base Sequence
- Cell Nucleus
(metabolism)
- Chromosomes, Human, Pair 15
(genetics)
- Coronary Artery Disease
(genetics, metabolism)
- Coronary Vessels
(metabolism)
- DNA-Binding Proteins
(chemistry, genetics, metabolism)
- Dimerization
- Endothelium, Vascular
(metabolism)
- Erythroid-Specific DNA-Binding Factors
- Female
- Fluorescent Antibody Technique
- GATA1 Transcription Factor
- Gene Expression
- Genes, Dominant
- Genetic Linkage
- Genetic Markers
- Genetic Predisposition to Disease
- Humans
- MADS Domain Proteins
- MEF2 Transcription Factors
- Male
- Middle Aged
- Molecular Sequence Data
- Muscle, Smooth
(cytology, metabolism)
- Myocardial Infarction
(genetics, metabolism)
- Myogenic Regulatory Factors
- Pedigree
- Protein Binding
- Protein Conformation
- Protein Structure, Tertiary
- Protein Transport
- Rats
- Risk Factors
- Sequence Deletion
- Signal Transduction
- Transcription Factors
(chemistry, genetics, metabolism)
- Transcriptional Activation
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