Minimally invasive aortic banding in mice: effects of altered cardiomyocyte insulin signaling during pressure overload
Minimally invasive aortic banding in mice: effects of altered cardiomyocyte insulin signaling during pressure overload
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DOI：
10.1152/ajpheart.00108.2003
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发表时间：
2003-09-01
影响因子：
4.8
通讯作者：
Litwin, SE
中科院分区：
文献类型：
--
作者：
Hu, P;Zhang, DF;Litwin, SE
我们开发了一种微创方法，用于在小鼠中产生左心室（LV）压力超负荷。通过使用这种技术，我们快速且可重复地捆扎横主动脉，手术发病率和死亡率较低。微创横主动脉环扎术（MTAB）会急性和慢性增加左心室收缩压，增加心脏重量与体重之比，并诱发心肌纤维化。我们使用这种技术来确定心脏中胰岛素信号传导的减少是否改变了心脏对压力超负荷的反应。心肌细胞限制性敲除胰岛素受体 (CIRKO) 的小鼠的心脏比野生型 (WT) 对照小鼠的心脏更小。 MTAB 后 4 周，WT 和 CIRKO 小鼠左室收缩压相对升高，心脏质量增加，β-肌球蛋白重链和心房钠尿因子 mRNA 诱导表达。然而，与 WT 小鼠相比，CIRKO 小鼠心脏扩张更严重，超声心动图显示左室收缩功能降低，间质纤维化程度更高。与 WT 心脏相比，带状 CIRKO 心脏中结缔组织生长因子的表达增加。因此，心脏中胰岛素信号传导的缺乏会加速心脏压力超负荷期间向更失代偿状态的转变。 MTAB 方法的使用应有助于压力超负荷肥大的病理生理学和治疗的研究。
We developed a minimally invasive method for producing left ventricular (LV) pressure overload in mice. With the use of this technique, we quickly and reproducibly banded the transverse aorta with low surgical morbidity and mortality. Minimally invasive transverse aortic banding (MTAB) acutely and chronically increased LV systolic pressure, increased heart weight-to-body weight ratio, and induced myocardial fibrosis. We used this technique to determine whether reduced insulin signaling in the heart altered the cardiac response to pressure overload. Mice with cardiac myocyte-restricted knockout of the insulin receptor (CIRKO) have smaller hearts than wild-type (WT) controls. Four weeks after MTAB, WT and CIRKO mice had comparably increased LV systolic pressure, increased cardiac mass, and induction of mRNA for beta-myosin heavy chain and atrial natriuretic factor. However, CIRKO hearts were more dilated, had depressed LV systolic function by echocardiography, and had greater interstitial fibrosis than WT mice. Expression of connective tissue growth factor was increased in banded CIRKO hearts compared with WT hearts. Thus lack of insulin signaling in the heart accelerates the transition to a more decompensated state during cardiac pressure overload. The use of the MTAB approach should facilitate the study of the pathophysiology and treatment of pressure-overload hypertrophy.