Variable phenotype in murine transverse aortic constriction.

Variable phenotype in murine transverse aortic constriction.
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DOI:
10.1016/j.carpath.2011.05.002
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发表时间:
2012-05
影响因子:
3.7
通讯作者:
Redfield, Margaret M.
Redfield, Margaret M.
中科院分区:
医学4区
文献类型:
--
作者:
Mohammed, Selma F.;Storlie, Jimmy R.;Oehler, Elise A.;Bowen, Lorna A.;Korinek, Josef;Lam, Carolyn S. P.;Simari, Robert D.;Burnett, John C., Jr.;Redfield, Margaret M.

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在小鼠中,横向主动脉缩窄(TAC)被认为是压力超负荷诱导的肥大(LVH)或心力衰竭(HF)的模型。虽然通常使用,但TAC模型中的可变性定义不好。本研究的目的是描述TAC模型的变异性,并定义一种简单的、非侵入性的方法,用于前瞻性地识别TAC后HF与代偿性LVH的小鼠。八周龄的雄性C57 BL/6 J小鼠经历TAC或假手术,然后在TAC后三周进行超声心动图。在三周超声心动图后处死一组SHAM和TAC小鼠,而其余小鼠在TAC后九周进行重复超声和处死。通过二维超声、解剖主动脉M型、彩色血流、横主动脉(TA)脉冲多普勒检查和左室收缩压(LVP)评估TAC的存在。在一个子集中有创地评估跨TAC压力梯度。HF定义为假手术小鼠的肺/体重>上限。与SHAM相比,TAC小鼠在TAC后3周或9周具有较高的TA速度、LVP和LV重量以及较低的射血分数(EF)。只有一部分TAC小鼠(28%)发生了HF。与代偿性LVH相比,HF小鼠的特征是相似的TA速度和较高的TA狭窄百分比,但LVP较低、LV重量较高、LV腔较大、EF较低和应力校正的中壁纤维缩短以及更多的纤维化。在TAC后3周通过超声心动图测量的EF和LV质量均可预测TAC后3周或9周HF的存在。在野生型小鼠中,TAC产生可变的心脏表型。TAC后三周超声心动图显示LV质量和EF的显著异常在尸检时鉴定为HF小鼠。这些数据与小鼠研究的适当设计和解释相关。
In mice, transverse aortic constriction (TAC) is variably characterized as a model of pressure overload induced hypertrophy (LVH) or heart failure (HF). While commonly used, variability in the TAC model is poorly defined. The objectives of this study were to characterize the variability in the TAC model and to define a simple, non-invasive method of prospectively identifying mice with HF versus compensated LVH after TAC. Eight week old, male C57BL/6J mice underwent TAC or SHAM and then echo at three weeks post-TAC. A group of SHAM and TAC mice were sacrificed after the three week echocardiogram, while the remainder underwent repeat echo and sacrifice at nine weeks post-TAC. The presence of TAC was assessed with 2 dimensional echo, anatomic aortic m-mode and color flow and pulsed-wave Doppler examination of the transverse aorta (TA) and by LV systolic pressure (LVP). Trans-TAC pressure gradient was assessed invasively in a subset. HF was defined as lung/body weight > upper limit in SHAM operated mice. As compared to SHAM, TAC mice had higher TA velocity, LVP and LV weight and lower ejection fraction (EF) at three or nine weeks post-TAC. Only a subset of TAC mice (28%) developed HF. As compared to compensated LVH, HF mice were characterized by similar TA velocity and higher percent TA stenosis, but lower LVP, higher LV weight, larger LV cavity, lower EF and stress-corrected midwall fiber shortening and more fibrosis. Both EF and LV mass measured by echo at three weeks post-TAC were predictive of the presence of HF at three or nine weeks post-TAC. In wild type mice, TAC produces a variable cardiac phenotype. Marked abnormalities in LV mass and EF at echo three weeks post-TAC identify mice with HF at autopsy. These data are relevant to appropriate design and interpretation of murine studies.
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