Department of Molecular Cardiovascular Biology, Yamaguchi University School of Medicine, Kurume, Japan.
Pathol Int. 2011 Oct;61(10):559-64. doi: 10.1111/j.1440-1827.2011.02699.x. Epub 2011 Jul 12.
Abdominal aortic aneurysm (AAA) is a common disease caused by segmental weakening of the aortic walls and progressive aortic dilation leading to the eventual rupture of the aorta. Currently no biomarkers have been established to indicate the disease status of AAA. Tenascin-C (TN-C) is a matricellular protein that is synthesized under pathological conditions. In the current study, we related TN-C expression to the clinical course and the histopathology of AAA to investigate whether the pattern of TN-C expression could indicate the status of AAA. We found that TN-C and matrix metalloproteinase (MMP)-9 were highly expressed in human AAA. In individual human AAA TN-C deposition associated with the tissue destruction, overlapped mainly with the smooth muscle actin-positive cells, and showed a pattern distinct from macrophages and MMP-9. In the mouse model of AAA high TN-C expression was associated with rapid expansion of the AAA diameter. Histological analysis revealed that TN-C was produced mainly by vascular smooth muscle cells and was deposited in the medial layer of the aorta during tissue inflammation and excessive destructive activities. Our findings suggest that TN-C may be a useful biomarker for indicating the pathological status of smooth muscle cells and interstitial cells in AAA.
腹主动脉瘤 (AAA) 是一种常见疾病,由主动脉壁的节段性弱化和进行性扩张导致主动脉最终破裂引起。目前尚无生物标志物可用于指示 AAA 的疾病状态。Tenascin-C (TN-C) 是一种基质细胞蛋白,在病理条件下合成。在本研究中,我们将 TN-C 的表达与 AAA 的临床过程和组织病理学相关联,以研究 TN-C 的表达模式是否可以指示 AAA 的状态。我们发现 TN-C 和基质金属蛋白酶 (MMP)-9 在人 AAA 中高度表达。在个体人 AAA 中,TN-C 沉积与组织破坏相关,主要与平滑肌肌动蛋白阳性细胞重叠,并呈现出与巨噬细胞和 MMP-9 不同的模式。在 AAA 的小鼠模型中,高 TN-C 表达与 AAA 直径的快速扩张相关。组织学分析显示,TN-C 主要由血管平滑肌细胞产生,并在组织炎症和过度破坏活动期间沉积在主动脉的中膜层。我们的研究结果表明,TN-C 可能是一种有用的生物标志物,可用于指示 AAA 中平滑肌细胞和间质细胞的病理状态。