Exposure to real-ambient particulate matter induced vascular hypertrophy through activation of PDGFRβ

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: PDGFRβ; Particulate matter; VSMCs; Vascular toxicity.