Jones Blain, Tonniges Jeffrey R, Debski Anna, Albert Benjamin, Yeung David A, Gadde Nikhit, Mahajan Advitiya, Sharma Neekun, Calomeni Edward P, Go Michael R, Hans Chetan P, Agarwal Gunjan
Department of Biomedical Engineering, The Ohio State University, Columbus, OH, USA.
Biophysics Graduate Program, The Ohio State University, Columbus, OH, USA.
Acta Biomater. 2020 Jul 1;110:129-140. doi: 10.1016/j.actbio.2020.04.022. Epub 2020 Apr 25.
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 SIGNIFICANCE: Several 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.
诸如腹主动脉瘤（AAA）之类的血管疾病的特征是血管壁发生剧烈重塑，并伴有弹性蛋白和胶原蛋白含量的变化。在大分子水平上，已有报道称AAA中的弹性纤维会发生显著的结构改变。虽然AAA中胶原纤维的波纹度（波状起伏）也会降低，但对于AAA以及其他血管病变中纤维亚水平上胶原原纤维的变化却知之甚少。在本研究中，我们调查了在血管手术时提取的人类AAA组织以及从输注血管紧张素II（AngII）的AAA ApoE小鼠模型中提取的主动脉中胶原原纤维的结构变化。使用透射电子显微镜和原子力显微镜检查胶原原纤维结构。对图像进行分析以确定D周期的长度和深度、原纤维直径和原纤维曲率。在切除的人体组织以及输注AngII的小鼠AAA重塑区域中观察到具有受损D周期条带的异常胶原原纤维。这些异常原纤维的特征是D周期深度在统计学上显著降低，并且胶原原纤维的曲率增加。与小鼠样本相比，这些特征在人类AAA中更为明显。输注AngII的小鼠的胸主动脉、输注生理盐水的小鼠的腹主动脉以及非AAA人类对照的腹主动脉均未含有异常胶原原纤维。异常胶原原纤维的结构改变似乎与其他组织中承受机械过载或慢性炎症的胶原原纤维所报道的改变相似。检测异常胶原可用于更好地了解血管以及其他病变中潜在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的特征是血管壁广泛重塑。虽然弹性纤维的结构改变在血管疾病中已得到充分表征，但对于这些疾病中的胶原原纤维结构却知之甚少。我们在此报告使用透射电子显微镜（TEM）和原子力显微镜（AFM）等高分辨率显微镜技术对AAA中的胶原原纤维进行的全面超微结构评估。我们阐明了在临床AAA以及小鼠模型的血管组织中如何存在具有受损D周期性和增加的原纤维曲率的异常胶原原纤维。我们讨论了这些异常胶原原纤维如何可能是AAA伴随的机械过载的结果，并可能影响潜在组织的功能特性。
