Collagen fibril abnormalities in human and mice abdominal aortic aneurysm
Collagen fibril abnormalities in human and mice abdominal aortic aneurysm
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DOI：
10.1016/j.actbio.2020.04.022
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发表时间：
2020-07-01
影响因子：
9.7
通讯作者：
Agarwal, Gunjan
中科院分区：
文献类型：
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作者：
Jones, Blain;Tonniges, Jeffrey R.;Agarwal, Gunjan
腹主动脉瘤（AAA）等血管疾病的特征是血管壁的剧烈重塑，伴随着弹性蛋白和胶原蛋白含量的变化。据报道，在大分子水平上，AAA的弹性蛋白纤维发生了显著的结构改变。虽然在AAA中胶原纤维的波动（波浪形）也减少了，但对AAA中亚纤维水平胶原纤维的变化以及其他血管病变知之甚少。在本研究中，我们研究了血管手术时提取的人AAA组织和注入ApoE（-/-）小鼠AAA模型中血管紧张素II （AngII）提取的主动脉中胶原纤维的结构变化，采用透射电镜和原子力显微镜观察胶原纤维结构。对图像进行分析，确定d -周期性的长度和深度、纤维直径和纤维曲率。在切除的人体组织和灌注AngII的小鼠的AAA重塑区域中，观察到d周期带受损的异常胶原原纤维。这些异常原纤维的特征是d期深度的显著减少和胶原原纤维曲率的增加。与小鼠样本相比，这些特征在人类AAA中更为明显。注射angii小鼠的胸主动脉、注射盐水小鼠的腹主动脉和非aaa人对照的腹主动脉均未发现异常的胶原原纤维。异常胶原原纤维的结构改变与其他组织中遭受机械负荷或慢性炎症的胶原原纤维的结构改变相似。检测异常胶原蛋白可以更好地了解血管和其他病变的细胞外基质的功能特性。包括腹主动脉瘤（AAA）在内的几种血管疾病以血管壁广泛重构为特征。虽然弹性蛋白纤维的结构改变在血管疾病中有很好的特征，但对这些疾病中的胶原纤维结构知之甚少。我们在此报告了一项全面的AAA胶原原纤维超微结构评估，使用高分辨率显微镜技术，如透射电子显微镜（TEM）和原子力显微镜（AFM）。我们阐明了在临床AAA和小鼠模型中，血管组织中存在d -周期性受损和纤维曲率增加的异常胶原原纤维。我们讨论了这些异常的胶原原纤维如何可能是AAA伴随的机械负荷的结果，并可能影响底层组织的功能特性。(C) 2020材料学报Elsevier Ltd.出版。版权所有。
Vascular diseases like abdominal aortic aneurysms (AAA) are characterized by a drastic remodeling of the vessel wall, accompanied with changes in the elastin and collagen content. At the macromolecular level, the elastin fibers in AAA have been reported to undergo significant structural alterations. While the undulations (waviness) of the collagen fibers is also reduced in AAA, very little is understood about changes in the collagen fibril at the sub-fiber level in AAA as well as in other vascular pathologies. In this study we investigated structural changes in collagen fibrils in human AAA tissue extracted at the time of vascular surgery and in aorta extracted from angiotensin II (AngII) infused ApoE(-/-) mouse model of AAA. Collagen fibril structure was examined using transmission electron microscopy and atomic force microscopy. Images were analyzed to ascertain length and depth of D-periodicity, fibril diameter and fibril curvature. Abnormal collagen fibrils with compromised D-periodic banding were observed in the excised human tissue and in remodeled regions of AAA in AngII infused mice. These abnormal fibrils were characterized by statistically significant reduction in depths of D-periods and an increased curvature of collagen fibrils. These features were more pronounced in human AAA as compared to murine samples. Thoracic aorta from Ang II-infused mice, abdominal aorta from saline-infused mice, and abdominal aorta from non-AAA human controls did not contain abnormal collagen fibrils. The structural alterations in abnormal collagen fibrils appear similar to those reported for collagen fibrils subjected to mechanical overload or chronic inflammation in other tissues. Detection of abnormal collagen could be utilized to better understand the functional properties of the underlying extracellular matrix in vascular as well as other pathologies.Statement of SignificanceSeveral vascular diseases including abdominal aortic aneurysm (AAA) are characterized by extensive remodeling in the vessel wall. Although structural alterations in elastin fibers are well characterized in vascular diseases, very little is known about the collagen fibril structure in these diseases. We report here a comprehensive ultrastructural evaluation of the collagen fibrils in AAA, using high-resolution microscopy techniques like transmission electron microscopy (TEM) and atomic force microscopy (AFM). We elucidate how abnormal collagen fibrils with compromised D-periodicity and increased fibril curvature are present in the vascular tissue in both clinical AAA as well as in murine models. We discuss how these abnormal collagen fibrils are likely a consequence of mechanical overload accompanying AAA and could impact the functional properties of the underlying tissue. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.