华中科技大学秦川小组报道了泡沫细胞衍生的外泌体通过将代谢缺陷传递给小胶质细胞而加剧缺血性白质损伤。相关论文于2025年5月8日发表于国际顶尖学术期刊《细胞—代谢》杂志上。

研究团队发现AS循环外泌体加重了缺血性白质损伤和VCI。源自巨噬细胞衍生泡沫细胞的外泌体靶向小胶质细胞。在机制上，泡沫细胞衍生的外泌体通过miR-101-3p-Nrf2-Slc2a1轴将氧化还原失衡、线粒体功能障碍和代谢缺陷传递给小胶质细胞。抗miR-101-3p或激活Nrf2，在遗传和药理学上都可以拮抗AS外泌体并改善VCI。总之，他们的发现揭示了外周巨噬细胞和脑小胶质细胞之间的遥远联系，这为AS诱导的VCI提供了新的见解和潜在的靶点。

据悉，动脉粥样硬化（AS）已被证明是血管性认知障碍（VCI）的独立危险因素，但其机制尚不清楚。

附：英文原文

Title: The foam cell-derived exosomes exacerbate ischemic white matter injury via transmitting metabolic defects to microglia

Author: Hang Zhang, Luo-Qi Zhou, Sheng Yang, Ming-Hao Dong, Lian Chen, Yi-Lin Lu, Lu-Yang Zhang, Lan Zhang, Yun-Hui Chu, Lu-Lu Xu, Xiao-Wei Pang, Li-Fang Zhu, Ting Xu, Tu-ying Yong, Wei Wang, Dai-Shi Tian, Chuan Qin

Issue&Volume: 2025-05-08

Abstract: Atherosclerosis (AS) has been shown to be an independent risk factor for vascular cognitive impairment (VCI), but the mechanisms remain unclear. Here, we found that AS circulating exosomes exacerbated ischemic white matter injury and VCI. Exosomes originating from macrophage-derived foam cells targeted microglia. Mechanistically, foam cell-derived exosomes transmitted redox imbalance, mitochondrial dysfunction, and metabolic defects to microglia via the miR-101-3p-Nrf2-Slc2a1 axis. Anti-miR-101-3p or activation of Nrf2, both genetically and pharmacologically, could antagonize AS exosomes and ameliorate VCI. In conclusion, our findings reveal a distant connection between peripheral macrophages and brain microglia, which provides new insights and potential targets of AS-induced VCI.

DOI: 10.1016/j.cmet.2025.04.009

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00219-0