Publication Date:
2003-12-03
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1618876/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1618876/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Lejin -- Fan, Chun -- Topol, Sarah E -- Topol, Eric J -- Wang, Qing -- R01 HL065630/HL/NHLBI NIH HHS/ -- R01 HL066251/HL/NHLBI NIH HHS/ -- R01 HL65630/HL/NHLBI NIH HHS/ -- R01 HL66251/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2003 Nov 28;302(5650):1578-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Cardiovascular Genetics, Department of Cardiovascular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14645853" target="_blank"〉PubMed〈/a〉
Keywords:
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
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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