A Rat Model of Pressure Overload Induced Moderate Remodeling and Systolic Dysfunction as Opposed to Overt Systolic Heart Failure.
A Rat Model of Pressure Overload Induced Moderate Remodeling and Systolic Dysfunction as Opposed to Overt Systolic Heart Failure.
复制标题
压力超负荷的大鼠模型会引起中度重塑和收缩功能障碍，而不是明显的收缩性心力衰竭。
DOI：
10.3791/60954
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发表时间：
2020-04-30
期刊：
影响因子：
--
通讯作者：
Delafontaine P
中科院分区：
文献类型：
--
作者：
Chaanine AH;Navar LG;Delafontaine P
响应于损伤，例如心肌梗塞、长期高血压或心脏毒性剂，心脏最初通过激活信号转导途径来适应，以在短期内抵消心肌细胞损失和/或壁应力的增加。然而，这些通路的长期激活变得有害，导致心脏重塑的启动和传播，从而导致左心室几何形状的变化和左心室容积的增加;这是收缩性心力衰竭（HF）患者中观察到的表型。在这里，我们描述了压力超负荷诱导的中度重塑和早期收缩功能障碍（MOD）的升主动脉束带（AAB）通过血管夹与内部面积为2平方毫米的大鼠模型的创建。手术在200 g Sprague-Dawley大鼠中进行。MOD HF表型在AAB后8-12周发展，并通过超声心动图进行非侵入性表征。先前的工作表明，激活信号转导途径和改变基因表达和翻译后修饰的蛋白质在MOD HF表型，模拟那些在人类收缩期HF中看到的，因此，使MOD HF表型的翻译研究，以确定和测试潜在的治疗抗重构目标的合适的模型在HF。与明显的收缩期HF表型相比，MOD HF表型的优势在于其允许鉴定参与早期重塑过程的分子靶标和早期应用治疗干预。MOD HF表型的局限性在于它可能无法模拟导致人类收缩期HF的疾病谱。此外，这是一个具有挑战性的表型，因为AAB手术与高死亡率和失败率相关，只有20%的手术大鼠发展出所需的HF表型。我们描述了压力超负荷诱导的中度重塑和早期收缩功能障碍的大鼠模型的创建，其中参与重塑过程的启动的信号转导通路被激活。这种动物模型将有助于确定分子靶点，用于心力衰竭的早期治疗性抗重塑策略。
In response to an injury, such as myocardial infarction, prolonged hypertension or a cardiotoxic agent, the heart initially adapts through the activation of signal transduction pathways, to counteract, in the short-term, for the cardiac myocyte loss and or the increase in wall stress. However, prolonged activation of these pathways becomes detrimental leading to the initiation and propagation of cardiac remodeling leading to changes in left ventricular geometry and increases in left ventricular volumes; a phenotype seen in patients with systolic heart failure (HF). Here, we describe the creation of a rat model of pressure overload induced moderate remodeling and early systolic dysfunction (MOD) by ascending aortic banding (AAB) via a vascular clip with an internal area of 2 mm2. The surgery is performed in 200 g Sprague-Dawley rats. The MOD HF phenotype develops at 8–12 weeks after AAB and is characterized noninvasively by means of echocardiography. Previous work suggests the activation of signal transduction pathways and altered gene expression and post-translational modification of proteins in the MOD HF phenotype that mimic those seen in human systolic HF; therefore, making the MOD HF phenotype a suitable model for translational research to identify and test potential therapeutic anti-remodeling targets in HF. The advantages of the MOD HF phenotype compared to the overt systolic HF phenotype is that it allows for the identification of molecular targets involved in the early remodeling process and the early application of therapeutic interventions. The limitation of the MOD HF phenotype is that it may not mimic the spectrum of diseases leading to systolic HF in human. Moreover, it is a challenging phenotype to create, as the AAB surgery is associated with high mortality and failure rates with only 20% of operated rats developing the desired HF phenotype. We describe the creation of a rat model of pressure overload induced moderate remodeling and early systolic dysfunction where signal transduction pathways involved in the initiation of the remodeling process are activated. This animal model will aid in identifying molecular targets for applying early therapeutic anti-remodeling strategies for heart failure.
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影响因子：
37.8
作者：
Kehat I;Molkentin JD
通讯作者：
Molkentin JD
DOI：
10.1152/ajpheart.00816.2006
发表时间：
2007-05-01
影响因子：
4.8
作者：
Barrick, Cordelia J.;Rojas, Mauricio;Threadgill, David W.
通讯作者：
Threadgill, David W.
DOI：
10.1161/circheartfailure.112.000200
发表时间：
2013-05
期刊：
Circulation. Heart failure
影响因子：
--
作者：
Chaanine AH;Gordon RE;Kohlbrenner E;Benard L;Jeong D;Hajjar RJ
通讯作者：
Hajjar RJ
DOI：
10.1152/ajpheart.00896.2008
发表时间：
2009-09-01
影响因子：
4.8
作者：
Barrick, Cordelia J.;Dong, Anping;Smyth, Susan S.
通讯作者：
Smyth, Susan S.
影响因子：
5.4
作者：
Chaanine AH;Sreekumaran Nair K;Bergen RH 3rd;Klaus K;Guenzel AJ;Hajjar RJ;Redfield MM
通讯作者：
Redfield MM