Medial Hypoxia and Adventitial Vasa Vasorum Remodeling in Human Ascending Aortic Aneurysm.
Medial Hypoxia and Adventitial Vasa Vasorum Remodeling in Human Ascending Aortic Aneurysm.
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DOI：
10.3389/fcvm.2018.00124
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发表时间：
2018
影响因子：
3.6
通讯作者：
Phillippi JA
中科院分区：
文献类型：
--
作者：
Billaud M;Hill JC;Richards TD;Gleason TG;Phillippi JA
人类升主动脉瘤特征性地表现出主动脉壁囊性内侧变性，包括弹性蛋白变性、蛋白聚糖积聚和平滑肌细胞损失。大多数研究都集中在主动脉中膜上，而对外膜层在人类动脉瘤疾病中的重要性的了解有限。我们最近证明，外膜 ECM 含有关键的血管生成因子，这些因子在主动脉瘤标本中下调。在这项研究中，我们研究了不同病因的动脉瘤主动脉标本的外膜微血管网络（血管滋养管），并假设升主动脉瘤患者的血管滋养管受到破坏。对苏木精和伊红染色的人主动脉横截面进行形态测量分析，揭示了动脉瘤标本中血管滋养管重塑的证据，包括血管密度降低、管腔面积增加和平滑肌肌动蛋白阳性层增厚。这些改变在二尖瓣主动脉瓣 (BAV) 相关主动脉病的标本中观察到的结果不一致，而血管滋养管重塑通常在形态正常的三尖瓣主动脉瓣 (TAV) 患者出现的动脉瘤中观察到。与非动脉瘤标本相比，动脉瘤标本外膜中缺氧诱导因子1α及其下游靶标金属硫蛋白1A和促血管生成因子血管内皮生长因子的基因表达下调，而抗血管生成因子血小板反应蛋白-1的水平升高。葡萄糖转运蛋白 1 (GLUT1) 是慢性组织缺氧的标志物，其免疫检测在非动脉瘤内侧标本中含量极低，并且在弹性蛋白变性区域局部积累，特别是在 TAV 相关动脉瘤中。 GLUT1 的定量显示，与非动脉瘤对应物相比，TAV 相关动脉瘤的主动脉中膜中的 GLUT1 水平升高。我们在动脉瘤标本中发现了慢性炎症的证据，即淋巴浆细胞浸润，与 BAV 患者相比，TAV 患者的动脉瘤标本中淋巴浆细胞浸润的发生率更高。这些数据强调了不同病因的动脉瘤之间血管滋养管重塑和相关内侧慢性缺氧标志物的差异。这些畸变可能导致主动脉中膜营养不良，并且可能参与胸主动脉瘤的发病机制。
Human ascending aortic aneurysms characteristically exhibit cystic medial degeneration of the aortic wall encompassing elastin degeneration, proteoglycan accumulation and smooth muscle cell loss. Most studies have focused on the aortic media and there is a limited understanding of the importance of the adventitial layer in the setting of human aneurysmal disease. We recently demonstrated that the adventitial ECM contains key angiogenic factors that are downregulated in aneurysmal aortic specimens. In this study, we investigated the adventitial microvascular network (vasa vasorum) of aneurysmal aortic specimens of different etiology and hypothesized that the vasa vasorum is disrupted in patients with ascending aortic aneurysm. Morphometric analyses of hematoxylin and eosin-stained human aortic cross-sections revealed evidence of vasa vasorum remodeling in aneurysmal specimens, including reduced density of vessels, increased lumen area and thickening of smooth muscle actin-positive layers. These alterations were inconsistently observed in specimens of bicuspid aortic valve (BAV)-associated aortopathy, while vasa vasorum remodeling was typically observed in aneurysms arising in patients with the morphologically normal tricuspid aortic valve (TAV). Gene expression of hypoxia-inducible factor 1α and its downstream targets, metallothionein 1A and the pro-angiogenic factor vascular endothelial growth factor, were down-regulated in the adventitia of aneurysmal specimens when compared with non-aneurysmal specimens, while the level of the anti-angiogenic factor thrombospondin-1 was elevated. Immunodetection of glucose transporter 1 (GLUT1), a marker of chronic tissue hypoxia, was minimal in non-aneurysmal medial specimens, and locally accumulated within regions of elastin degeneration, particularly in TAV-associated aneurysms. Quantification of GLUT1 revealed elevated levels in the aortic media of TAV-associated aneurysms when compared to non-aneurysmal counterparts. We detected evidence of chronic inflammation as infiltration of lymphoplasmacytic cells in aneurysmal specimens, with a higher prevalence of lymphoplasmacytic infiltrates in aneurysmal specimens from patients with TAV compared to that of patients with BAV. These data highlight differences in vasa vasorum remodeling and associated medial chronic hypoxia markers between aneurysms of different etiology. These aberrations could contribute to malnourishment of the aortic media and could conceivably participate in the pathogenesis of thoracic aortic aneurysm.
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影响因子：
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DOI：
10.1161/hypertensionaha.115.06262
发表时间：
2016-05
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
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