Department of Medical Physiology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Division of Vascular Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Curr Drug Targets. 2018;19(11):1327-1332. doi: 10.2174/1389450119666180122154409.
An abdominal aortic aneurysm (AAA), which affects approximately 10% of Japanese men aged ≥ 65 years, is frequently associated with hypertension, dyslipidemia, and other lifestyle- related diseases. The development of an AAA is attributed to chronic inflammation concomitant with arteriosclerotic changes. However, an accurate pathomechanism associated with AAA remains uncertain, and questions such as why only a particular group/percentage of patients with arteriosclerosis develop aneurysms and how diabetes suppresses aneurysm development remain unanswered.
We examined a novel mechanism to develop AAA based on histopathological findings following analysis of the human AAA tissues. Additionally, based on these findings, we developed a new animal model of AAA, in which the histopathological characteristics are similar to human AAA tissue.
Recently, we identified stenosis of the vasa vasorum (VV) in aortic segments showing dilatation. The aorta is the largest artery in our circulatory system. Under physiological conditions, the inner layer of the aorta is nourished via direct diffusion of nutrients from the luminal blood flow, whereas the outer adventitia is primarily perfused by the VV. Therefore, hypoperfusion of the VV induces hypoxia and subsequent inflammation and tissue degeneration of the aortic wall, resulting in aneurysm formation. Based on these findings, we established an AAA animal model by reducing the blood flow through the VV to the aortic wall. AAA was successfully reproduced in our animal model. Histopathological findings in this model were indistinguishable from those observed in humans, and pronounced abnormality in lipid composition in blood vessel adventitia was also observed.
Thus, hypoperfusion of the aortic wall appeared to be sufficient to cause inflammationinduced AAA. These findings may provide potential targets for novel therapeutics for the management of an AAA.
腹主动脉瘤（AAA）影响了约 10%的 65 岁以上的日本男性，常与高血压、血脂异常和其他生活方式相关疾病有关。AAA 的发展归因于伴有动脉粥样硬化变化的慢性炎症。然而，与 AAA 相关的确切发病机制尚不清楚，一些问题仍然没有答案，例如为什么只有特定的一组/百分比的动脉粥样硬化患者会发展为动脉瘤，以及糖尿病如何抑制动脉瘤的发展。
我们根据对人类 AAA 组织的分析，从组织病理学的发现来研究一种新的 AAA 发病机制。此外，基于这些发现，我们开发了一种新的 AAA 动物模型，其组织病理学特征与人类 AAA 组织相似。
最近，我们发现主动脉扩张段的血管腔（VV）狭窄。主动脉是我们循环系统中最大的动脉。在生理条件下，主动脉的内层通过从管腔血流中直接扩散的营养物质得到滋养，而外膜主要由 VV 灌注。因此，VV 的灌注不足会导致缺氧，随后引起主动脉壁的炎症和组织退化，导致动脉瘤形成。基于这些发现，我们通过减少 VV 向主动脉壁的血流来建立 AAA 动物模型。我们的动物模型成功地复制了 AAA。该模型的组织病理学发现与人类观察到的结果无法区分，并且还观察到血管外膜中脂质组成的明显异常。
因此，主动脉壁的灌注不足似乎足以引起炎症诱导的 AAA。这些发现可能为 AAA 的管理提供新的治疗靶点。
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