Tenascin-C is expressed in abdominal aortic aneurysm tissue with an active degradation process
Tenascin-C is expressed in abdominal aortic aneurysm tissue with an active degradation process
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DOI：
10.1111/j.1440-1827.2011.02699.x
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发表时间：
2011-10-01
影响因子：
2.2
通讯作者：
Matsuzaki, Masunori
中科院分区：
文献类型：
--
作者：
Kimura, Taizo;Yoshimura, Koichi;Matsuzaki, Masunori
腹主动脉瘤（AAA）是一种常见的疾病，由主动脉壁的节段性弱化和进行性主动脉扩张引起，最终导致主动脉破裂。目前尚未建立指示AAA疾病状态的生物标志物。腱生蛋白-C（Tenascin-C，TN-C）是在病理条件下合成的基质细胞蛋白。在本研究中，我们将TN-C表达与AAA的临床病程和组织病理学联系起来，以探讨TN-C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，并显示出与巨噬细胞和MMP-9不同的模式。在AAA小鼠模型中，TN-C高表达与AAA直径的快速扩张相关。组织学分析表明，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时沉积在主动脉的中层。提示TN-C可能是一种反映AAA中平滑肌细胞和间质细胞病理状态的有用生物标志物。
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.