Elevated blood pressure and enhanced myocardial contractility in mice with severe IGF-1 deficiency
Elevated blood pressure and enhanced myocardial contractility in mice with severe IGF-1 deficiency
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DOI：
10.1172/jci119086
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发表时间：
1996-12-01
影响因子：
15.9
通讯作者：
PowellBraxton, L
中科院分区：
文献类型：
--
作者：
Lembo, G;Rockman, HA;PowellBraxton, L
为了避免胰岛素样生长因子1（IGF-1）完全缺乏的胚胎致死性，我们为特定位点插入事件产生突变的IGF-1等位基因（igf1(m)）产生小鼠纯合子。这些小鼠的IGF-1水平为野生型的30%，但存活到成年，因此可以对表型进行生理分析。小型化导管技术显示IGF-1小鼠的意识血压升高（m/m），左心室收缩力测量值增加。在IGF-1（m/m）心脏中腺苷酸环化酶活性增强，而β -肾上腺素能受体密度没有增加，这表明IGF-1和β -肾上腺素能信号通路之间的串扰可能介导了收缩性的增加。然而，在IGF-1（m/m）小鼠中，左心室心肌对主动脉收缩的肥厚反应被保留。我们得出结论，IGF-1水平的慢性改变可以选择性地调节血压和左心室功能，而不影响体内适应性心肌肥大。
To circumvent the embryonic lethality of a complete deficiency in insulin-like growth factor 1 (IGF-1), we generated mice homozygous for a site-specific insertional event that created a mutant IGF-1 allele (igf1(m)). These mice have IGF-1 levels 30% of wild type yet survive to adulthood, thereby allowing physiological analysis of the phenotype. Miniaturized catheterization technology revealed elevated conscious blood pressure in IGF-1(m/m) mice, and measurements of left ventricular contractility were increased. Adenylyl cyclase activity was enhanced in IGF-1(m/m) hearts, without an increase in beta-adrenergic receptor density, suggesting that crosstalk between IGF-1 and beta-adrenergic signaling pathways may mediate the increased contractility. The hypertrophic response of the left ventricular myocardium in response to aortic constriction, however, was preserved in IGF-1(m/m) mice. We conclude that chronic alterations in IGF-1 levels can selectively modulate blood pressure and left ventricular function, while not affecting adaptive myocardial hypertrophy in vivo.