Polystyrene nanoplastics accelerate atherosclerosis: Unraveling the impact on smooth muscle cells through KIF15-mediated migration

Autor: Yizhou Zhong, Yu Feng, Yuji Huang, Bo Wang, Wenting Shi, Boxuan Liang, Zhiming Li, Bingli Zhang, Jiaxin Du, Jiancheng Xiu, Xingfen Yang, Zhenlie Huang
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Ecotoxicology and Environmental Safety, Vol 284, Iss , Pp 116983- (2024)
Druh dokumentu: article
ISSN: 0147-6513
DOI: 10.1016/j.ecoenv.2024.116983
Popis: Microplastics and nanoplastics (MNPs) originating from plastic pollution pose potential threats to cardiovascular health, with prior studies linking MNPs to atherosclerosis. Our earlier research elucidated how nanoplastics enhance macrophages' phagocytic activity, leading to the formation of foam cells and an elevated risk of atherosclerosis. However, the specific influence of MNPs on smooth muscle cells (SMCs) in the context of MNP-induced atherosclerosis remains poorly understood. In this study, ApoE knockout (ApoE-/-) male mice with a high-fat diet were orally exposed to environmentally realistic concentrations of 2.5–250 mg/kg polystyrene nanoplastics (PS-NPs, 50 nm) for consecutive 19 weeks. Cardiovascular toxicity was comprehensively assessed through histopathological, transcriptomic, and proteomic analyses, while mechanisms underlying this toxicity were explored through in vitro studies. Herein, hematoxylin and eosin staining revealed accelerated atherosclerotic plaque development in ApoE-/- mice exposed to PS-NPs. Multi-omics analysis identified kinesin family member 15 (KIF15) as a pivotal target molecule. Both in vitro and in vivo experiments affirmed the specific upregulation of KIF15 in mouse aortic SMCs exposed to PS-NPs. Furthermore, in vitro experiments demonstrated that PS-NPs can promote the migration ability of MOVAS cells. Knockdown of Kif15 revealed its role in reducing MOVAS cell migration, with subsequent exposure to PS-NPs reversing the increased migration ability. This suggests that PS-NPs promote SMC migration by upregulating KIF15, and the migration of SMCs is closely associated with atherosclerosis outcomes. This study significantly advances our understanding of MNP-induced cardiovascular toxicity, providing valuable insights for risk assessment of human MNP exposure.
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