Spatiotemporal mapping of matrix remodelling and evidence of in situ elastogenesis in experimental abdominal aortic aneurysms.

Spatiotemporal mapping of matrix remodelling and evidence of in situ elastogenesis in experimental abdominal aortic aneurysms.
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DOI:
10.1002/term.1905
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发表时间:
2017-01
影响因子:
3.3
通讯作者:
Ramamurthi, Anand
Ramamurthi, Anand
中科院分区:
工程技术3区
文献类型:
--
作者:
Deb, Partha Pratim;Ramamurthi, Anand

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研究了弹性蛋白酶诱导的大鼠腹主动脉瘤(AAA)细胞外基质(ECM)的时空变化。在诱导后7、14和21d,根据AAA组织相对于肾动脉的位置和最大主动脉内径区域,将AAA组织分为近端、中端和远端。AAA空间区之间的室壁厚度有显著差异,最初由于阳性基质重塑而增加,然后由于管壁变薄和基质致密而随着疾病的进展而减少。使用自定义分割工具分析的组织学图像显示,与健康组织相比,AAA空间区之间的ECM成分和结构以及基质重塑的程度和性质存在显著差异。组织学和免疫荧光(IF)标记提供了以弹性蛋白纤维存在为特征的新内膜AAA重塑的证据。这种重塑是由平滑肌α-肌动蛋白阳性的新生内膜细胞影响的,透射电子显微镜显示这种细胞在形态上与中膜SMCs不同。新生内膜的透射电子显微镜进一步显示无定形弹性蛋白的细长沉积和新生但未成熟的弹性纤维。这些结构似乎缺乏至少一种微纤维成分--原纤素-1,这是成熟弹性纤维组装的关键。我们在AAA新生内膜中观察到大量弹性蛋白和弹性纤维样结构的产生,这在AAA组织中的其他地方没有观察到,这为我们提供了一个独特的机会来利用这种自我再生现象,并从基质组织的角度将其引导到恢复健康的主动脉基质结构、力学和功能上。
Spatio-temporal changes in the extracellular matrix (ECM) were studied within abdominal aortic aneurysms (AAA) generated in rats via elastase-infusion. At 7, 14, and 21 days post-induction, AAA tissues were divided into proximal, mid and distal regions based on their location relative to the renal arteries and region of maximal aortic diameter. Wall thicknesses differed significantly between the AAA spatial regions, initially increasing due to positive matrix remodeling, and then decreasing due to wall thinning and compaction of matrix as the disease progressed. Histological images analyzed using custom segmentation tools indicated significant differences in ECM composition and structure, versus healthy tissue and in the extent and nature of matrix remodeling, between the AAA spatial regions. Histology and immunofluorescence (IF) labeling provided evidence of neointimal AAA remodeling characterized by presence of elastin-containing fibers. This remodeling was effected by smooth muscle alpha actin-positive neointimal cells that transmission electron microscopy (TEM) showed to morphologically differ from medial SMCs. TEM of the neointima further showed presence of elongated deposits of amorphous elastin and presence of nascent, but not mature elastic fibers. These structures appeared to be deficient in at least one microfibrillar component, fibrillin-1, which is critical to mature elastic fiber assembly. The substantial production of elastin and elastic fiber-like structures that we observed in the AAA neointima, which was not observed elsewhere within AAA tissues, provides us a unique opportunity to capitalize on this auto-regenerative phenomenon and direct it from the standpoint of matrix organization towards restoring healthy aortic matrix structure, mechanics, and function.
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