Cerebral amyloid angiopathy (CAA) is a disease in which amyloid β (Aβ) is deposited in the cerebral blood vessels, reducing compliance, tearing and weakening of vessels’ walls, leading to cerebral hemorrhage. The mechanisms by which Aβ leads to focal wall fragmentation and intimal damage are not well understood. We analyzed the motility of human brain microvascular endothelial cells (hBMECs) in real-time using a wound-healing assay. We observed the suppression of cell migration by visualizing Aβ aggregation using quantum dot (QD) nanoprobes. In addition, using QD nanoprobes and a SiR-actin probe, we simultaneously observed Aβ aggregation and F-actin organization in real-time for the first time. Aβ began to aggregate at the edge of endothelial cells, reducing cell motility. In addition, Aβ aggregation disorganized the actin cytoskeleton and induced abnormal actin aggregation. Aβ aggregated actively in the anterior group, where cell motility was active. Our findings may be a first step toward explaining the mechanism by which Aβ causes vascular wall fragility, bleeding, and rebleeding in CAA.

中文翻译：

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β淀粉样蛋白通过破坏肌动蛋白细胞骨架来干扰脑微血管内皮细胞的伤口愈合


脑淀粉样血管病（CAA）是β淀粉样蛋白（Aβ）沉积在脑血管中，导致顺应性降低、血管壁撕裂和弱化，导致脑出血的疾病。 Aβ 导致局灶壁破碎和内膜损伤的机制尚不清楚。我们使用伤口愈合试验实时分析人脑微血管内皮细胞 (hBMEC) 的运动性。我们通过使用量子点 (QD) 纳米探针可视化 Aβ 聚集来观察细胞迁移的抑制情况。此外，使用QD纳米探针和SiR-肌动蛋白探针，我们首次同时实时观察Aβ聚集和F-肌动蛋白组织。 Aβ开始在内皮细胞边缘聚集，降低细胞运动性。此外，Aβ聚集扰乱肌动蛋白细胞骨架并诱导异常肌动蛋白聚集。 Aβ 在前组中聚集活跃，细胞运动活跃。我们的研究结果可能是解释 Aβ 导致 CAA 血管壁脆性、出血和再出血机制的第一步。