Severe coronary artery stenoses and reduced coronary flow velocity reserve in atherosclerotic mouse model Doppler echocardiography validation study
Severe coronary artery stenoses and reduced coronary flow velocity reserve in atherosclerotic mouse model Doppler echocardiography validation study
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DOI：
10.1016/j.atherosclerosis.2007.12.019
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发表时间：
2008-09-01
期刊：
影响因子：
5.3
通讯作者：
Knuuti, Juhani
中科院分区：
文献类型：
--
作者：
Saraste, Antti;Kyto, Ville;Knuuti, Juhani
目的：转基因高脂血症小鼠越来越多地被用作动脉粥样硬化的动物模型，但其冠状动脉疾病的特征仍然很差。此外，用于检测冠状动脉病变的功能后果的非侵入性工具仍有待在小鼠中进行测试。经胸多普勒超声心动图测定冠状动脉血流速度储备（CFVR）可作为评价冠状动脉狭窄程度的血流动力学指标。因此，我们应用多普勒超声心动图在动脉粥样硬化小鼠研究CFVR和组织学确定的冠状动脉narrowing.Methods之间的关系：动脉粥样硬化LDLR/ApoB 48双基因敲除小鼠58-72周龄（n=12）和年龄匹配的C57 BL/6小鼠（n=5）进行了研究。在腺苷诱导的最大血管舒张过程中，通过多普勒超声心动图测量麻醉小鼠左冠状动脉（LCA）中段的CFVR。结果：LDLR/ApoB 48双基因敲除小鼠的近端和中部LCA均出现动脉粥样硬化病变，但中部LCA未见动脉粥样硬化病变，导致不同程度的管腔狭窄（30-97%）。对照组未见病变。与对照组相比，动脉粥样硬化小鼠的CFVR显著降低（2.3 +/- 0.5 vs. 1.7 +/- 0.5，p=0.02）。CFVR与管腔狭窄量呈负相关（r=-0.91，p=0.001）。平均CFVR在狭窄>= 70%的小鼠中始终低于狭窄< 70%的小鼠（1.3 +/- 0.1，n=7对2.2 +/- 0.4，n=5，p = 0.0002）。CFVR降低是这些病变的一致特征。冠状动脉血流的多普勒超声心动图可用于检测活体动脉粥样硬化小鼠的限流性狭窄。(C)2007爱思唯尔爱尔兰有限公司保留所有权利。
Objective: Genetically modified hyperlipidemic mice are increasingly used as an animal model of atherosclerosis, but their coronary artery disease remains poorly characterized. Furthermore, non-invasive tools to detect functional consequences of coronary lesions remain to be tested in mice. Coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography provides a hemodynamic measure of coronary artery stenosis severity in humans. Thus, we applied Doppler echocardiography in atherosclerotic mice to study the relationship between CFVR and histologically determined coronary artery narrowing.Methods: Atherosclerotic LDLR/ApoB48 double knockout mice of 58-72 weeks age (n=12) and age-matched C57BL/6 mice (n=5) were studied. CFVR was measured in anesthetized mice by Doppler echocardiography in the middle left coronary artery (LCA) during adenosine-induced maximal vasodilatation. Histopathology of proximal and middle LCA was studied in serial tissue sections.Results: All LDLR/ApoB48 double knockout mice had atherosclerotic lesions in the proximal, but not in the middle LCA causing various degrees of luminal narrowing (30-97%). No lesions were found in controls. Compared with controls, CFVR was significantly reduced in the atherosclerotic mice (2.3 +/- 0.5 vs. 1.7 +/- 0.5, p=0.02). There was a negative correlation between CFVR and the amount of luminal narrowing (r=-0.91, p=0.001). Average CFVR was consistently lower in mice that had >= 70% than < 70% stenosis (1.3 +/- 0.1, n=7 vs. 2.2 +/- 0.4, n=5, p = 0.0002).Conclusions: LDLR/ApoB48 double knockout mice are characterized with histologically severe coronary artery narrowings. Reduced CFVR is a consistent feature of these lesions. Doppler echocardiography of coronary artery flow can be used to detect flow-limiting stenosis in living atherosclerotic mice. (C) 2007 Elsevier Ireland Ltd. All rights reserved.