Medin 是一种常见的血管淀粉样蛋白生成肽，最近与阿尔茨海默病 (AD) 和血管性痴呆有关，其病理学仍不清楚。我们的目标是确定暴露于 Medin 的人脑微血管内皮细胞 (HBMVEC) 转录组谱和通路的变化，将其与暴露于 β-淀粉样蛋白 (Aβ) 进行比较，并评估含有单唾液酸神经节苷脂的纳米脂质体 (NL) 的保护作用。将 HBM​​VEC 暴露于不含或含有 Aβ(1-42) (2 µM) 或 NL (300 µg/mL) 的 Medin (5 µM) 中 20 小时，并进行 RNA-seq 和信号通路分析。另外，在用 Medin (5 µM) 处理的 HBMVEC 中进行选择的已识别基因的逆转录聚合酶链反应，不加或加 NFκB 抑制剂 RO106-9920 (10 µM) 或 NL (300 µg/mL)。 Medin 引起促炎基因的上调，Aβ42 联合治疗不会加剧这种情况，但 NL 可以逆转这种情况。对差异表达基因的通路分析揭示了多种促炎信号通路，例如肿瘤坏死因子（TNF）和核因子-κB（NFkB）信号通路，特别受到medin治疗的影响。 RO106-9920 和 NL 减少 medin 诱导的促炎激活。 Medin 部分通过 NFκB 诱导内皮细胞促炎信号传导，而 NL 可逆转该信号传导。这可能对血管老化、AD 和血管性痴呆的发病机制和治疗产生潜在影响。© 2023。这是美国政府的作品，在美国不受版权保护；可能适用外国版权保护。

Medin is a common vascular amyloidogenic peptide recently implicated in Alzheimer's disease (AD) and vascular dementia and its pathology remains unknown. We aim to identify changes in transcriptomic profiles and pathways in human brain microvascular endothelial cells (HBMVECs) exposed to medin, compare that to exposure to β-amyloid (Aβ) and evaluate protection by monosialoganglioside-containing nanoliposomes (NL). HBMVECs were exposed for 20 h to medin (5 µM) without or with Aβ(1-42) (2 µM) or NL (300 µg/mL), and RNA-seq with signaling pathway analyses were performed. Separately, reverse transcription polymerase chain reaction of select identified genes was done in HBMVECs treated with medin (5 µM) without or with NFκB inhibitor RO106-9920 (10 µM) or NL (300 µg/mL). Medin caused upregulation of pro-inflammatory genes that was not aggravated by Aβ42 co-treatment but reversed by NL. Pathway analysis on differentially expressed genes revealed multiple pro-inflammatory signaling pathways, such as the tumor necrosis factor (TNF) and the nuclear factor-κB (NFkB) signaling pathways, were affected specifically by medin treatment. RO106-9920 and NL reduced medin-induced pro-inflammatory activation. Medin induced endothelial cell pro-inflammatory signaling in part via NFκB that was reversed by NL. This could have potential implications in the pathogenesis and treatment of vascular aging, AD and vascular dementia.© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.