A mouse model of reverse cardiac remodelling following banding-debanding of the ascending aorta
A mouse model of reverse cardiac remodelling following banding-debanding of the ascending aorta
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DOI：
10.1111/j.1748-1716.2011.02369.x
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发表时间：
2012-05-01
影响因子：
6.3
通讯作者：
Tonnessen, T.
中科院分区：
文献类型：
--
作者：
Bjornstad, J. L.;Skrbic, B.;Tonnessen, T.
目的：压力超负荷期间的心肌重塑可能导致心力衰竭的发生。逆重塑通常发生在因主动脉瓣狭窄而进行主动脉瓣置换术之后。然而，逆向重塑的细节和调控机制仍然未知。因此，逆向重塑的实验模型将允许研究这一过程。尽管主动脉结扎模型被广泛使用，但关于解带模型的报道很少。本研究的目的是通过高分辨率超声心动图重复仔细评估血流动力学，建立小鼠的结扎解带模型。方法：对C57Bl/6小鼠进行升主动脉结扎和随后的解带。通过超声心动图评估心脏的几何形状和功能，并通过组织学和实时定量聚合酶链反应对左心室心肌进行分析。结果：通过无创估计梯度来控制主动脉环带的程度，我们发现超声心动图估计的左心室质量与处死时的体重之间存在密切相关性。主动脉束带导致左心室肥厚、纤维化和胎儿基因表达，表明心肌重塑。超声心动图显示同心左心室重构和心肌功能障碍。通过不同切口进行解带后，14 天时左心室重量迅速消退，心脏几何形状和功能正常化。结论：我们建立了一种可重复且经过仔细表征的升主动脉解带逆向重塑小鼠模型。这样的模型可能有助于增进对心脏病理学可逆性的理解，进而可能产生心力衰竭治疗的新策略。
Aim: Myocardial remodelling during pressure overload might contribute to development of heart failure. Reverse remodelling normally occurs following aortic valve replacement for aortic stenosis; however, the details and regulatory mechanisms of reverse remodelling remain unknown. Thus, an experimental model of reverse remodelling would allow for studies of this process. Although models of aortic banding are widely used, only few reports of debanding models exist. The aim of this study was to establish a bandingdebanding model in the mouse with repetitive careful haemodynamic evaluation by high-resolution echocardiography.Methods: C57Bl/6 mice were subjected to ascending aortic banding and subsequent debanding. Cardiac geometry and function were evaluated by echocardiography, and left ventricular myocardium was analysed by histology and quantitative real-time polymerase chain reaction.Results: The degree of aortic banding was controlled by non-invasive estimation of the gradient, and we found a close correlation between left ventricular mass estimated by echocardiography and weight at the time of killing. Aortic banding led to left ventricular hypertrophy, fibrosis and expression of foetal genes, indicating myocardial remodelling. Echocardiography revealed concentric left ventricular remodelling and myocardial dysfunction. Following debanding, performed via a different incision, there was rapid regression of left ventricular weight and normalization of both cardiac geometry and function by 14 days.Conclusions: We have established a reproducible and carefully characterized mouse model of reverse remodelling by banding and debanding of the ascending aorta. Such a model might contribute to increased understanding of the reversibility of cardiac pathology, which in turn might give rise to new strategies in heart failure treatment.