Bao Hongxu, Li Benying, You Qing, Dun Xinyu, Zhang Zhen, Liang Yanan, Li Yahui, Jiang Qixiao, Zhang Rong, Chen Rui, Chen Wen, Zheng Yuxin, Li Daochuan, Cui Lianhua
Department of Toxicology, School of Public Health, Qingdao University, Qingdao, China.
Department of Toxicology, School of Public Health, Hebei Medical University, Shijiazhuang, China.
J Hazard Mater. 2023 May 5;449:130985. doi: 10.1016/j.jhazmat.2023.130985. Epub 2023 Feb 11.
Vascular toxicity induced by particulate matter (PM) exposure exacerbates the onset and development of cardiovascular diseases; however, its detailed mechanism remains unclear. Platelet-derived growth factor receptor β (PDGFRβ) acts as a mitogen for vascular smooth muscle cells (VSMCs) and is therefore essential for normal vasoformation. However, the potential effects of PDGFRβ on VSMCs in PM-induced vascular toxicity have not yet been elucidated.
To reveal the potential roles of PDGFRβ signalling in vascular toxicity, individually ventilated cage (IVC)-based real-ambient PM exposure system mouse models and PDGFRβ overexpression mouse models were established in vivo, along with in vitro VSMCs models.
Vascular hypertrophy was observed following PM-induced PDGFRβ activation in C57/B6 mice, and the regulation of hypertrophy-related genes led to vascular wall thickening. Enhanced PDGFRβ expression in VSMCs aggravated PM-induced smooth muscle hypertrophy, which was attenuated by inhibiting the PDGFRβ and janus kinase 2 /signal transducer and activator of transcription 3 (JAK2/STAT3) pathways.
Our study identified the PDGFRβ gene as a potential biomarker of PM-induced vascular toxicity. PDGFRβ induced hypertrophic effects through the activation of the JAK2/STAT3 pathway, which may be a biological target for the vascular toxic effects caused by PM exposure.
接触颗粒物（PM）所诱导的血管毒性会加剧心血管疾病的发生和发展；然而，其详细机制仍不清楚。血小板衍生生长因子受体β（PDGFRβ）作为血管平滑肌细胞（VSMC）的促有丝分裂原，因此对正常血管形成至关重要。然而，PDGFRβ在PM诱导的血管毒性中对VSMC的潜在影响尚未阐明。
为了揭示PDGFRβ信号在血管毒性中的潜在作用，在体内建立了基于独立通气笼（IVC）的真实环境PM暴露系统小鼠模型和PDGFRβ过表达小鼠模型，以及体外VSMC模型。
在C57/B6小鼠中，PM诱导的PDGFRβ激活后观察到血管肥大，肥大相关基因的调控导致血管壁增厚。VSMC中PDGFRβ表达增强加剧了PM诱导的平滑肌肥大，通过抑制PDGFRβ和janus激酶2/信号转导和转录激活因子3（JAK2/STAT3）途径可使其减弱。
我们的研究确定PDGFRβ基因是PM诱导血管毒性的潜在生物标志物。PDGFRβ通过激活JAK2/STAT3途径诱导肥大效应，这可能是PM暴露引起血管毒性作用的生物学靶点。
