Pathophysiology of abdominal aortic aneurysms - Insights from the elastase-induced model in mice with different genetic backgrounds
Pathophysiology of abdominal aortic aneurysms - Insights from the elastase-induced model in mice with different genetic backgrounds
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DOI：
10.1196/annals.1383.029
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发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Pham, Christine T. N.
中科院分区：
文献类型：
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作者：
Thompson, Robert W.;Curci, John A.;Pham, Christine T. N.
腹主动脉瘤（AAA）是一种复杂的退行性疾病，涉及慢性主动脉壁炎症和结构结缔组织的破坏性重塑。使用人类AAA组织的研究有助于识别各种分子介质和基质降解蛋白酶，这些介质和基质降解蛋白酶有助于动脉瘤疾病，从而为理解AAA提供了坚实的基础;然而，这些人类组织标本仅代表长期和进行性疾病过程的“终末期”。因此，在理解AAAs的病理生理学方面的进一步进展部分取决于有效动物模型的开发和应用，这些模型概括了疾病的关键方面。基于大鼠的原始研究，用猪胰弹性蛋白酶短暂灌注腹主动脉提供了一种可重现且稳健的AAA模型。最近，这种模型在小鼠身上的应用也为研究开辟了新的途径。在这篇综述中，我们总结了调查使用弹性蛋白酶诱导的小鼠模型的AAAs，包括在动物中有针对性地删除特定的基因和更普遍的差异，在不同的遗传背景的小鼠的结果。这些研究帮助我们确定了对AAA发展至关重要的基因（如MMP 9，IL 6和AT 1 R），并揭示了可能在动脉瘤形成中起作用的其他基因。对来自不同遗传背景的小鼠的研究也开始提供一种新的方法来评估动脉瘤发展易感性的遗传基础。
Abdominal aortic aneurysms (AAAs) represent a complex degenerative disorder involving chronic aortic wall inflammation and destructive remodeling of structural connective tissue. Studies using human AAA tissues have helped identify a variety of molecular mediators and matrix-degrading proteinases, which contribute to aneurysm disease, thereby providing a sound foundation for understanding AAAs; however, these human tissue specimens represent only the "end stage" of a long and progressive disease process. Further progress in understanding the pathophysiology of AAAs is therefore dependent in part on the development and application of effective animal models that recapitulate key aspects of the disease. Based on original studies in rats, transient perfusion of the abdominal aorta with porcine pancreatic elastase has provided a reproducible and robust model of AAAs. More recent applications of this model to mice have also opened new avenues for investigation. In this review, we summarize investigations using the elastase-induced mouse model of AAAs including results in animals with targeted deletion of specific genes and more general differences in mice on different genetic backgrounds. These studies have helped us identify genes that are essential to the development of AAAs (such as MMP9, IL6, and AT1R) and to reveal other genes that may be dispensable in aneurysm formation. Investigations on mice from different genetic backgrounds are also beginning to offer a novel approach to evaluate the genetic basis for susceptibility to aneurysm development.