Polystyrene nanoplastics induce cardiotoxicity by upregulating HIPK2 and activating the P53 and TGF-β1/Smad3 pathways

• Published in: Journal of hazardous materials Vol. 474; p. 134823
• Main Authors: Yang, Jian-Zheng, Zhang, Kai-Kai, Hsu, Clare, Miao, Lin, Chen, Li-Jian, Liu, Jia-Li, Li, Jia-Hao, Li, Xiu-Wen, Zeng, Jia-Hao, Chen, Long, Li, Ji-Hui, Xie, Xiao-Li, Wang, Qi
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 05.08.2024
• Subjects: Cardiotoxicity; Homeodomain interacting protein kinase 2; P53 signaling pathway; Polystyrene nanoplastics; TGF-β1/Smad3 signaling pathway; P53 signaling pathway; Cardiotoxicity; Homeodomain interacting protein kinase 2; TGF-β1/Smad3 signaling pathway; Polystyrene nanoplastics
• ISSN: 0304-3894; 1873-3336; 1873-3336
• DOI: 10.1016/j.jhazmat.2024.134823

Nanoplastics (NPs) pollution has become a global environmental problem, raising numerous health concerns. However, the cardiotoxicity of NPs exposure and the underlying mechanisms have been understudied to date. To address this issue, we comprehensively evaluated the cardiotoxicity of polystyrene nanoplastics (PS-NPs) in both healthy and pathological states. Briefly, mice were orally exposed to four different concentrations (0 mg/day, 0.1 mg/day, 0.5 mg/day, and 2.5 mg/day) of 100-nm PS-NPs for 6 weeks to assess their cardiotoxicity in a healthy state. Considering that individuals with underlying health conditions are more vulnerable to the adverse effects of pollution, we further investigated the cardiotoxic effects of PS-NPs on pathological states induced by isoprenaline. Results showed that PS-NPs induced cardiomyocyte apoptosis, cardiac fibrosis, and myocardial dysfunction in healthy mice and exacerbated cardiac remodeling in pathological states. RNA sequencing revealed that PS-NPs significantly upregulated homeodomain interacting protein kinase 2 (HIPK2) in the heart and activated the P53 and TGF-beta signaling pathways. Pharmacological inhibition of HIPK2 reduced P53 phosphorylation and inhibited the activation of the TGF-β1/Smad3 pathway, which in turn decreased PS-NPs-induced cardiotoxicity. This study elucidated the potential mechanisms underlying PS-NPs-induced cardiotoxicity and underscored the importance of evaluating nanoplastics safety, particularly for individuals with pre-existing heart conditions. [Display omitted] ●Exposure to PS-NPs induces cardiotoxicity in a dose-dependent manner.●PS-NPs exacerbate cardiac apoptosis and fibrosis in pathological states.●PS-NPs upregulate HIPK2 and activate the P53 and TGF-β1/Smad3 pathways.●Inhibition of HIPK2 contributes to protection against PS-NPs-induced cardiotoxicity.