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通过原子力显微镜、免疫荧光和光学显微镜对ApoE基因敲除小鼠的局部动脉粥样硬化斑块特性进行定量分析。

Regional atherosclerotic plaque properties in ApoE-/- mice quantified by atomic force, immunofluorescence, and light microscopy.

作者信息

Hayenga H N, Trache A, Trzeciakowski J, Humphrey J D

机构信息

Department of Biomedical Engineering, Texas A&M University, College Station, TX, USA.

出版信息

J Vasc Res. 2011;48(6):495-504. doi: 10.1159/000329586. Epub 2011 Aug 11.

DOI:10.1159/000329586
PMID:21832839
Abstract

Elucidating regional material properties of arterial tissue is fundamental to predicting transmural stresses and understanding how tissue stiffness influences cellular responses and vice versa. Atomic force microscopy (AFM) was used to measure point-wise the axial compressive stiffness of healthy aortas and atherosclerotic plaques at micron level separation distances. Cross sections of plaques were obtained from a widely used animal model of atherosclerosis (ApoE-/- mice). Median point-wise values of material stiffness were 18.7 and 1.5 kPa for the unloaded healthy wall (n = 25 specimens) and plaque (n = 18), respectively. When the healthy wall was distended uniformly during AFM testing, two mechanically distinct populations emerged from comparisons of normal cumulative distributions, with median values of 9.8 and 76.7 kPa (n = 16). The higher values of stiffness may have been due to extended elastin, which was not present in the plaques. Rather, most plaques were identified via standard and immunofluorescent histology to be largely lipid laden, and they exhibited a nearly homogeneous linear elastic behavior over the small AFM indentations. Understanding the mechanics and mechanobiological factors involved in lesion development and remodeling could lead to better treatments for those lesions that are vulnerable to rupture.

摘要

阐明动脉组织的区域材料特性对于预测跨壁应力以及理解组织刚度如何影响细胞反应(反之亦然)至关重要。原子力显微镜(AFM)用于在微米级分离距离下逐点测量健康主动脉和动脉粥样硬化斑块的轴向压缩刚度。斑块的横截面取自一种广泛使用的动脉粥样硬化动物模型(ApoE - / - 小鼠)。对于未加载的健康壁(n = 25个标本)和斑块(n = 18),材料刚度的逐点中值分别为18.7和1.5 kPa。在AFM测试期间,当健康壁均匀扩张时,通过正常累积分布的比较出现了两个机械特性不同的群体,中值分别为9.8和76.7 kPa(n = 16)。较高的刚度值可能是由于弹性蛋白伸展,而斑块中不存在这种情况。相反,大多数斑块通过标准和免疫荧光组织学鉴定为主要充满脂质,并且在小的AFM压痕上表现出几乎均匀的线性弹性行为。了解病变发展和重塑过程中涉及的力学和机械生物学因素可能会为那些易破裂的病变带来更好的治疗方法。

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