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特发性退行性胸主动脉瘤与主动脉中层淀粉样变性有关。

Idiopathic degenerative thoracic aneurysms are associated with increased aortic medial amyloid.

机构信息

a Institute of Integrative Biology, University of Liverpool , Liverpool , UK.

b Computational Biology Facility, Technology Directorate, University of Liverpool , Liverpool , UK.

出版信息

Amyloid. 2019 Sep;26(3):148-155. doi: 10.1080/13506129.2019.1625323. Epub 2019 Jun 18.

Abstract

To explore the relationship of aortic medial amyloid with biochemical and micromechanical properties of the aortic wall in aneurysm patients. Human aortic tissues removed during aneurysm surgery from tricuspid (idiopathic degenerative aneurysm, DA) and bicuspid valve (BAV) patients were subjected to oscillatory nanoindentation experiments to determine localised mechanical properties of the tissue (shear storage modulus, ´ and shear loss modulus, ˝). Collagen, elastin, matrix metalloproteinase 2 and glycosaminoglycans concentrations were determined, along with relative levels of aortic medial amyloid-related factors (medin, milk fat globule-EGF factor 8, oligomers and fibrils). Measurements were combined with clinical data and statistical analyses performed. The DA cohort can be divided based on their phenotype. One group shared similar characteristics with BAV patients, termed bicuspid like phenotype-tricuspid valve. The second group had high amyloid oligomer species present with a significantly lower ´ ( = .01), indicative of reduced elastic response of the tissue, termed amyloid-rich. We identified a group of DA patients with high amyloid oligomers and altered micromechanical and structural properties of the vessel wall. We propose these findings as a cause for aneurysm formation in these patients. Amyloid is not found in BAV patients, suggesting at least two distinct mechanisms for pathogenesis.

摘要

探讨主动脉中层淀粉样变与动脉瘤患者主动脉壁生化和微观力学特性的关系。从三尖瓣(特发性退行性动脉瘤,DA)和二叶瓣(BAV)患者的动脉瘤手术中取出人主动脉组织,进行振荡纳米压痕实验,以确定组织的局部力学特性(剪切储能模量,´和剪切损耗模量,˝)。测定胶原、弹性蛋白、基质金属蛋白酶 2 和糖胺聚糖的浓度,以及与主动脉中层淀粉样变相关因子(medin、乳脂肪球 EGF 因子 8、寡聚物和纤维)的相对水平。将测量结果与临床数据相结合,并进行统计分析。可以根据 DA 队列的表型进行分组。一组与 BAV 患者具有相似的特征,称为二叶瓣样表型-三尖瓣。第二组存在大量的淀粉样寡聚物,´显著降低(= 0.01),表明组织弹性反应降低,称为富含淀粉样蛋白。我们鉴定出一组 DA 患者具有高淀粉样寡聚物和血管壁微观力学及结构特性改变。我们认为这些发现是这些患者动脉瘤形成的原因。BAV 患者中未发现淀粉样蛋白,这表明至少存在两种不同的发病机制。

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