Distinct Phenotypes Induced by Three Degrees of Transverse Aortic Constriction in Mice
Distinct Phenotypes Induced by Three Degrees of Transverse Aortic Constriction in Mice
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DOI：
10.1038/s41598-019-42209-7
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发表时间：
2019-04-10
影响因子：
4.6
通讯作者：
Blanton, Robert M.
中科院分区：
文献类型：
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作者：
Richards, Daniel A.;Aronovitz, Mark J.;Blanton, Robert M.
横断主动脉缩窄（TAC）是小鼠压力过载引起的心脏肥厚和衰竭的一种成熟模型。收缩“紧度”的程度决定了TAC的严重程度，并由所用针的量规(G)决定。尽管许多报告使用TAC模型，但很少有研究直接比较了结果表型的范围。在这项研究中，成年雄性小鼠随机接受轻度（25G）、中度（26G）或重度（27G）不同松紧程度的TAC手术，持续4周，同时进行假手术对照。每周超声心动图和终末血流动力学测量确定心脏重构和功能。与假小鼠相比，所有TAC模型均诱导显著的严重依赖性左心室肥厚和舒张功能障碍。26G TAC组小鼠还表现出轻微的收缩功能障碍和心脏纤维化，而27G TAC组小鼠有更严重的收缩和舒张功能障碍，严重的心脏纤维化，更容易表现出心力衰竭的特征，如血浆BNP升高。在没有肾脏结构、功能或基因表达改变的情况下，我们还观察到27G TAC小鼠的肾脏萎缩。25G、26G和27G TAC在心脏结构和功能方面产生不同的反应。这些不同的表型可能在不同的临床前环境中有用。
Transverse aortic constriction (TAC) is a well-established model of pressure overload-induced cardiac hypertrophy and failure in mice. The degree of constriction "tightness" dictates the TAC severity and is determined by the gauge (G) of needle used. Though many reports use the TAC model, few studies have directly compared the range of resulting phenotypes. In this study adult male mice were randomized to receive TAC surgery with varying degrees of tightness: mild (25G), moderate (26G) or severe (27G) for 4 weeks, alongside sham-operated controls. Weekly echocardiography and terminal haemodynamic measurements determined cardiac remodelling and function. All TAC models induced significant, severity-dependent left ventricular hypertrophy and diastolic dysfunction compared to sham mice. Mice subjected to 26G TAC additionally exhibited mild systolic dysfunction and cardiac fibrosis, whereas mice in the 27G TAC group had more severe systolic and diastolic dysfunction, severe cardiac fibrosis, and were more likely to display features of heart failure, such as elevated plasma BNP. We also observed renal atrophy in 27G TAC mice, in the absence of renal structural, functional or gene expression changes. 25G, 26G and 27G TAC produced different responses in terms of cardiac structure and function. These distinct phenotypes may be useful in different preclinical settings.