Time-Dependent Pathological Changes in Hypoperfusion-Induced Abdominal Aortic Aneurysm.
Time-Dependent Pathological Changes in Hypoperfusion-Induced Abdominal Aortic Aneurysm.
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DOI：
10.3390/biology10020149
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发表时间：
2021-02-14
期刊：
影响因子：
4.2
通讯作者：
Zaima N
中科院分区：
文献类型：
--
作者：
Kugo H;Sukketsiri W;Tanaka H;Fujishima R;Moriyama T;Zaima N
腹主动脉瘤(AAA)是一种腹主动脉逐渐扩张的血管疾病，因破裂死亡率高。动脉壁供血系统血管阻塞导致的低灌注率可能是AAA病理生理过程中的重要因素。时间依赖性分析对于了解主动脉壁低灌流后的病理性级联反应非常重要。在我们的研究中，使用低灌流诱导的动物模型进行的时间依赖分析表明，许多氨基酸相关因子的动态变化可能与低氧诱导因子-1α水平的增加有关。血管狭窄引起的低灌注率可能是AAA治疗的一个新的药物靶点。血管狭窄引起的低灌注率可导致室壁缺氧和腹主动脉瘤(AAA)。尽管低灌注量是AAA病理改变的重要因素，但低灌注量与AAA之间的相关性尚不完全清楚。本研究对低灌注性主动脉壁改变进行了时间相关的半定量病理分析，以了解主动脉壁逐渐退化导致AAA形成的机制。根据动态变化的时间将AAA相关因子分为五组：第一组：血管紧张素II1型受体、内皮素-1和丙二醛；第二组：基质金属蛋白酶-2、-9、-12、M1巨噬细胞(Mac387+细胞)和单核细胞趋化蛋白-1；第三组：合成平滑肌细胞(SMCs)；第四组：中性粒细胞弹性蛋白酶、收缩的SMCs和血管紧张素原；第五组：M2巨噬细胞(CD163+细胞)。缺氧诱导因子-1α、ET-1、丙二醛和基质金属蛋白酶-9在3h内与α-平滑肌肌动蛋白细胞共定位，提示低灌流诱导的低氧直接影响腹主动脉瘤早期收缩的平滑肌细胞的活性。时间依赖性病理分析阐明了AAA相关因素的级联作用。这些发现为理解AAA复杂的多阶段病理机制提供了线索。
Abdominal aortic aneurysm (AAA) is a vascular disease that involves gradual dilation of the abdominal aorta and has a high mortality due to rupture. Hypoperfusion due to the obstruction of vasa vasorum, which is a blood supply system in the aortic wall, may be an important factor involved in AAA pathophysiology. A time-dependent analysis is important to understand the pathological cascade following hypoperfusion in the aortic wall. In our study, time-dependent analysis using a hypoperfusion-induced animal model showed that the dynamics of many AAA-related factors might be associated with the increased hypoxia-inducible factor-1α level. Hypoperfusion due to stenosis of the vasa vasorum might be a new drug target for AAA therapeutics. Hypoperfusion due to vasa vasorum stenosis can cause wall hypoxia and abdominal aortic aneurysm (AAA) development. Even though hypoperfusion is an important contributor toward pathological changes in AAA, the correlation between hypoperfusion and AAA is not fully understood. In this study, a time-dependent semi-quantitative pathological analysis of hypoperfusion-induced aortic wall changes was performed to understand the mechanisms underlying the gradual degradation of the aortic wall leading to AAA formation. AAA-related factors evaluated in this study were grouped according to the timing of dynamic change, and five groups were formed as follows: first group: angiotensin II type 1 receptor, endothelin-1 (ET-1), and malondialdehyde (MDA); second group: matrix metalloproteinase (MMP)-2, -9, -12, M1 macrophages (Mac387+ cells), and monocyte chemotactic protein-1; third group: synthetic smooth muscle cells (SMCs); fourth group: neutrophil elastase, contractile SMCs, and angiotensinogen; and the fifth group: M2 macrophages (CD163+ cells). Hypoxia-inducible factor-1α, ET-1, MDA, and MMP-9 were colocalized with alpha-smooth muscle actin cells in 3 h, suggesting that hypoperfusion-induced hypoxia directly affects the activities of contractile SMCs in the initial stage of AAA. Time-dependent pathological analysis clarified the cascade of AAA-related factors. These findings provide clues for understanding complicated multistage pathologies in AAA.
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