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腹主动脉瘤动物模型的转化相关性及最新进展

Translational Relevance and Recent Advances of Animal Models of Abdominal Aortic Aneurysm.

作者信息

Sénémaud Jean, Caligiuri Giuseppina, Etienne Harry, Delbosc Sandrine, Michel Jean-Baptiste, Coscas Raphaël

机构信息

From the UMR 1148, Inserm-Paris7 - Denis Diderot University, Xavier Bichat Hospital, Paris, France (J.S., G.C., H.E., S.D., J.-B.M., R.C.); UMR 1173, Inserm-Paris11 - Faculty of Health Sciences Simone Veil, Versailles Saint-Quentin-en-Yvelines University, Paris-Saclay University, Montigny-le-Bretonneux, France (R.C.); Department of Vascular Surgery, Ambroise Paré University Hospital, AP-HP, Boulogne-Billancourt, France (R.C.); and UMR 1018, Inserm-Paris11 - CESP, Versailles Saint-Quentin-en-Yvelines University, Paris-Saclay University, Paul Brousse Hospital, Villejuif, France (R.C.).

出版信息

Arterioscler Thromb Vasc Biol. 2017 Mar;37(3):401-410. doi: 10.1161/ATVBAHA.116.308534. Epub 2017 Jan 5.

Abstract

UNLABELLED

Human abdominal aortic aneurysm (AAA) pathophysiology is not yet completely understood. In conductance arteries, the insoluble extracellular matrix, synthesized by vascular smooth muscle cells, assumes the function of withstanding the intraluminal arterial blood pressure. Progressive loss of this function through extracellular matrix proteolysis is a main feature of AAAs. As most patients are now treated via endovascular approaches, surgical AAA specimens have become rare. Animal models provide valuable complementary insights into AAA pathophysiology. Current experimental AAA models involve induction of intraluminal dilation (nondissecting AAAs) or a contained intramural rupture (dissecting models). Although the ideal model should reproduce the histological characteristics and natural history of the human disease, none of the currently available animal models perfectly do so. Experimental models try to represent the main pathophysiological determinants of AAAs: genetic or acquired defects in extracellular matrix, loss of vascular smooth muscle cells, and innate or adaptive immune response. Nevertheless, most models are characterized by aneurysmal stabilization and healing after a few weeks because of cessation of the initial stimulus. Recent studies have focused on ways to optimize existing models to allow continuous aneurysmal growth. This review aims to discuss the relevance and recent advances of current animal AAA models.

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摘要

未标注

人类腹主动脉瘤(AAA)的病理生理学尚未完全明晰。在传导动脉中,由血管平滑肌细胞合成的不溶性细胞外基质承担着承受管腔内动脉血压的功能。通过细胞外基质蛋白水解导致该功能的逐渐丧失是腹主动脉瘤的主要特征。由于现在大多数患者通过血管内方法进行治疗,手术切除的腹主动脉瘤标本已变得稀少。动物模型为腹主动脉瘤的病理生理学提供了有价值的补充见解。当前的实验性腹主动脉瘤模型包括诱导管腔内扩张(非夹层腹主动脉瘤)或局限性壁内破裂(夹层模型)。尽管理想的模型应重现人类疾病的组织学特征和自然病程,但目前可用的动物模型均无法完美做到这一点。实验模型试图体现腹主动脉瘤的主要病理生理决定因素:细胞外基质的遗传或后天缺陷、血管平滑肌细胞的丧失以及先天性或适应性免疫反应。然而,大多数模型的特点是在最初刺激停止后几周内动脉瘤稳定并愈合。最近的研究集中在优化现有模型以实现动脉瘤持续生长的方法上。本综述旨在讨论当前动物腹主动脉瘤模型的相关性和最新进展。

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