Rao Jayashree, Brown Bryan N, Weinbaum Justin S, Ofstun Emily L, Makaroun Michel S, Humphrey Jay D, Vorp David A
Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pa.
Department of Bioengineering, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pa.
J Vasc Surg. 2015 Sep;62(3):585-93. doi: 10.1016/j.jvs.2014.11.086. Epub 2015 Jul 20.
Little is known about the etiologic factors that lead to the occurrence of intraluminal thrombus (ILT) during abdominal aortic aneurysm (AAA) development. Recent work has suggested that macrophages may play an important role in progression of a number of other vascular diseases, including atherosclerosis; however, whether these cells are present within the ILT of a progressing AAA is unknown. The purpose of this work was to define the presence, phenotype, and spatial distribution of macrophages within the ILT excised from six patients. We hypothesized that the ILT contains a population of activated macrophages with a distinct, nonclassical phenotypic profile.
ILT samples were examined using histologic staining and immunofluorescent labeling for multiple markers of activated macrophages (cluster of differentiation [CD]45, CD68, human leukocyte antigen-DR, matrix metalloproteinase 9) and the additional markers α-smooth muscle actin, CD34, CD105, fetal liver kinase-1, and collagen I and III.
Histologic staining revealed a distinct laminar organization of collagen within the shoulder region of the ILT lumen and a spatially heterogeneous cell composition within the ILT. Most of the cellular constituents of the ILT were in the luminal region and predominantly expressed markers of activated macrophages but also concurrently expressed α-smooth muscle actin, CD105, and synthesized collagen I and III.
This report presents evidence for the presence of a distinct macrophage population within the luminal region of AAA ILT. These cells express a set of markers indicative of a unique population of activated macrophages. The exact contributions of these previously unrecognized cells to ILT formation and AAA pathobiology remains unknown.
对于腹主动脉瘤(AAA)发展过程中导致腔内血栓(ILT)形成的病因因素知之甚少。最近的研究表明,巨噬细胞可能在包括动脉粥样硬化在内的许多其他血管疾病的进展中起重要作用;然而,这些细胞是否存在于进展期AAA的ILT内尚不清楚。本研究的目的是确定从6例患者切除的ILT内巨噬细胞的存在情况、表型和空间分布。我们假设ILT包含一群具有独特、非经典表型特征的活化巨噬细胞。
使用组织学染色和免疫荧光标记对ILT样本进行检测,以检测活化巨噬细胞的多种标志物(分化簇[CD]45、CD68、人类白细胞抗原-DR、基质金属蛋白酶9)以及其他标志物α-平滑肌肌动蛋白、CD34、CD105、胎儿肝激酶-1和I型及III型胶原蛋白。
组织学染色显示,ILT管腔肩部区域的胶原蛋白呈明显的分层结构,且ILT内细胞组成在空间上存在异质性。ILT的大多数细胞成分位于管腔区域,主要表达活化巨噬细胞的标志物,但同时也表达α-平滑肌肌动蛋白、CD105,并合成I型和III型胶原蛋白。
本报告提供了证据,表明AAA的ILT管腔区域存在独特的巨噬细胞群体。这些细胞表达一组标志物,表明它们是独特的活化巨噬细胞群体。这些先前未被认识的细胞对ILT形成和AAA病理生物学的确切贡献仍然未知。