Rapid degeneration of cultured human brain pericytes by amyloid beta protein.
Rapid degeneration of cultured human brain pericytes by amyloid beta protein.
复制标题
淀粉样β蛋白导致培养的人脑周细胞快速变性。
DOI：
10.1046/j.1471-4159.1997.68031135.x
复制
发表时间：
1997
影响因子：
4.7
通讯作者：
VanNostrand,WE
中科院分区：
文献类型：
--
作者：
Verbeek,MM;deWaal,RM;Schipper,JJ;VanNostrand,WE
淀粉样β蛋白（Aβ）沉积在脑动脉和毛细血管壁中是阿尔茨海默病和遗传性脑出血伴淀粉样变性-荷兰型（HCHWA-D）患者脑的主要特征之一。血管Aβ沉积伴随着平滑肌细胞和周细胞的变性。在这项研究中，我们发现携带“Dutch”突变（HCHWA‐D Aβ1-40）的Aβ1- 40以及野生型Aβ1- 42可诱导培养的人脑周细胞和人软脑膜平滑肌细胞变性，而野生型Aβ1- 40和HCHWA‐D Aβ1- 42无活性。培养的脑周细胞似乎比软脑膜平滑肌细胞更容易受到Aβ诱导的变性的影响，因为在暴露于HCHWA‐D Aβ1-40 2天后，脑周细胞培养物中的细胞活力已经降低，而在软脑膜平滑肌细胞培养物中，细胞死亡仅在4-5天后才显著。此外，在HCHWA‐D Aβ1-40短期处理后，软脑膜平滑肌细胞培养物的恢复能力优于脑周细胞培养物。任何一种细胞类型的变性之前，细胞淀粉样前体蛋白的产生增加。淀粉样蛋白结合染料刚果红可抑制细胞死亡和淀粉样蛋白前体蛋白的产生，表明Aβ的原纤维组装对于启动其破坏性作用至关重要。这些数据表明Aβ在诱导血管周围细胞病理学方面具有重要作用，如在阿尔茨海默病或HCHWA-D患者的脑血管中观察到的。
Amyloid β protein (Aβ) deposition in the cerebral arterial and capillary walls is one of the major characteristics of brains from patients with Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis‐Dutch type (HCHWA‐D). Vascular Aβ deposition is accompanied by degeneration of smooth muscle cells and pericytes. In this study we found that Aβ1–40carrying the “Dutch” mutation (HCHWA‐D Aβ1–40) as well as wild‐type Aβ1–42induced degeneration of cultured human brain pericytes and human leptomeningeal smooth muscle cells, whereas wild‐type Aβ1–40and HCHWA‐D Aβ1–42were inactive. Cultured brain pericytes appeared to be much more vulnerable to Aβ‐induced degeneration than leptomeningeal smooth muscle cells, because in brain pericyte cultures cell viability already decreased after 2 days of exposure to HCHWA‐D Aβ1–40, whereas in leptomeningeal smooth muscle cell cultures cell death was prominent only after 4–5 days. Moreover, leptomeningeal smooth muscle cell cultures were better able to recover than brain pericyte cultures after short‐term treatment with HCHWA‐D Aβ1–40. Degeneration of either cell type was preceded by an increased production of cellular amyloid precursor protein. Both cell death and amyloid precursor protein production could be inhibited by the amyloid‐binding dye Congo red, suggesting that fibril assembly of Aβ is crucial for initiating its destructive effects. These data imply an important role for Aβ in inducing perivascular cell pathology as observed in the cerebral vasculature of patients with Alzheimer's disease or HCHWA‐D.