Signs of cross-seeding: aortic medin amyloid as a trigger for protein AA deposition
Signs of cross-seeding: aortic medin amyloid as a trigger for protein AA deposition
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DOI：
10.3109/13506129.2011.630761
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发表时间：
2011-12-01
影响因子：
5.5
通讯作者：
Westermark, Per
中科院分区：
文献类型：
--
作者：
Larsson, Annika;Malmstrom, Susanna;Westermark, Per
系统性淀粉样病变所表现出的高度多样化的沉积模式，有时在同一种淀粉样病变中，仍未得到解释。在几乎所有50岁以上的个体中，局限性中质（AMed）淀粉样变由前体蛋白乳粘蛋白发展而来，沉积在胸主动脉中。鉴于其在人群中的高患病率，以及系统性淀粉样变也沉积在主动脉的事实，我们研究了AMed淀粉样蛋白是否会影响血清淀粉样蛋白A衍生（AA）淀粉样变的组织分布。研究了7例系统性AA淀粉样变患者的主动脉。当用双标记免疫荧光检测时，4个显示medin和AA聚集体之间的部分共定位。此外，体外研究表明，AMed淀粉样原纤维促进蛋白AA聚集成原纤维。研究结果表明，高频率的“老年性”淀粉样变可能通过交叉播种机制启动更不常见的淀粉样变的原纤维形成。
The highly diverse deposition pattern displayed by systemic amyloidoses, sometimes within the same amyloid disease, remains unexplained. The localized medin (AMed) amyloidosis develops from the precursor protein lactadherin and deposits in the media of the thoracic aorta in almost all individuals above 50 years of age. Given its high prevalence in the population, and the fact that systemic amyloidoses also deposit in the aorta, led us to investigate whether AMed amyloid could influence the tissue distribution of serum amyloid A derived (AA) amyloidosis. Seven aortas from patients with diagnosed systemic AA amyloidosis were investigated. Four displayed partial co-localization between medin and AA aggregates when examined with double-labeling immunofluorescence. Furthermore, in vitro studies showed that AMed amyloid-like fibrils promote the aggregation of protein AA into fibrils. The findings indicate that the highly frequent "senile" amyloidoses may have the potential to initiate fibril formation of the more uncommon amyloidoses by a cross-seeding mechanism.