Zhao Tianyang, Zhang Yuezhu, Li Xu, Ge Zhili, Shi Jingjing, Wang Tianyou, Zhang Jiaxin, Zhang Xinyu, Jiang Huibin, Zhou Liting, Ye Lin
Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, China.
Environ Toxicol. 2025 Apr;40(4):683-693. doi: 10.1002/tox.24461. Epub 2024 Dec 13.
Fine particulate matter (PM) can exacerbate the instability of atherosclerotic plaques although the exact chemical process driving atherosclerosis remains unknown. In order to create atherosclerotic models, a high-fat diet and vitamin D3 injections were given to 56 Wistar rats in this investigation. The atherosclerotic rats were split into four groups at random and given different doses of PM (0, 1.5, 7.5, and 37.5 mg/kg) for 4 weeks. To investigate the mechanism, foam cells were exposed to PM (0, 25, 50, and 100 μg/mL) for 24 h. The results showed that PM exposure caused collagen fibers thinner and muscle fibers were disorganized. PM exposure significantly affected the expression of MMP2, MMP9, TIMP2, and vimentin in aortas of atherosclerotic rats. Moreover, PM exposure increased the expression of the Notch signaling pathways which was correlated with the expression of atherosclerotic plaque stability-related genes. PM exposure also increased the apoptosis rate of foam cells. The expression of MMP2, MMP9, and vimentin was increased and TIMP2 was decreased with the increasing PM dose in foam cells. The inhibition of the Notch signaling pathway can alleviate the alteration of atherosclerotic plaque stability-related genes. The findings demonstrated that PM exposure can cause atherosclerotic plaques to become unstable, aggravating the progression of atherosclerosis, a process in which the Notch signaling pathway is crucial.
细颗粒物（PM）可加剧动脉粥样硬化斑块的不稳定性，尽管驱动动脉粥样硬化的确切化学过程尚不清楚。在本研究中，为了建立动脉粥样硬化模型，给56只Wistar大鼠喂食高脂饮食并注射维生素D3。将动脉粥样硬化大鼠随机分为四组，给予不同剂量的PM（0、1.5、7.5和37.5mg/kg），持续4周。为了研究其机制，将泡沫细胞暴露于PM（0、25、50和100μg/mL）中24小时。结果表明，暴露于PM会导致胶原纤维变细，肌纤维紊乱。PM暴露显著影响动脉粥样硬化大鼠主动脉中MMP2、MMP9、TIMP2和波形蛋白的表达。此外，PM暴露增加了Notch信号通路的表达，这与动脉粥样硬化斑块稳定性相关基因的表达相关。PM暴露还增加了泡沫细胞的凋亡率。在泡沫细胞中，随着PM剂量的增加，MMP2、MMP9和波形蛋白的表达增加，而TIMP2的表达降低。抑制Notch信号通路可减轻动脉粥样硬化斑块稳定性相关基因的改变。研究结果表明，暴露于PM可导致动脉粥样硬化斑块变得不稳定，加剧动脉粥样硬化的进展，在这一过程中Notch信号通路至关重要。
