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标题：Progressive hypertrophy and heart failure in β1-adrenergic receptor transgenic mice
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作者：Stefan Engelhardt ; Lutz Hein ; Frank Wiesmann 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1999
卷号：96
期号：12
页码：7059-7064
DOI：10.1073/pnas.96.12.7059
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Stimulation of cardiac {beta}1-adrenergic receptors is the main mechanism that increases heart rate and contractility. Consequently, several pharmacological and gene transfer strategies for the prevention of heart failure aim at improving the function of the cardiac {beta}-adrenergic receptor system, whereas current clinical treatment favors a reduction of cardiac stimulation. To address this controversy, we have generated mice with heart-specific overexpression of {beta}1-adrenergic receptors. Their cardiac function was investigated in organ bath experiments as well as in vivo by cardiac catheterization and by time-resolved NMR imaging. The transgenic mice had increased cardiac contractility at a young age but also developed marked myocyte hypertrophy (3.5-fold increase in myocyte area). This increase was followed by progressive heart failure with functional and histological deficits typical for humans with heart failure. Contractility was reduced by {approx}50% in 35-week-old mice, and ejection fraction was reduced down to a minimum of {approx}20%. We conclude that overexpression of {beta}1-adrenergic receptors in the heart may lead to a short-lived improvement of cardiac function, but that increased {beta}1-adrenergic receptor signalling is ultimately detrimental.