It is widely acknowledged that cardiovascular diseases constitute the leading cause of global mortality (Bikbov et al., 2020). Vascular remodelling is considered a crucial mechanism underlying the development of various vascular diseases, such as atherosclerosis and in-stent restenosis (Shi et al., 2019). Neointimal hyperplasia (NIH) characterised by arterial tunica intima thickening, is a common feature of vascular remodelling disorders (Ma et al., 2023). Vascular smooth muscle cells (VSMCs) exhibit quiescent and contractile phenotypes under normal conditions and remarkable phenotypic plasticity (Liu et al., 2015). VSMCs dedifferentiate from the contractile to the synthetic phenotype and are characterised by over-proliferation and migration from the media into the intima upon vascular injury (Basatemur et al., 2019; Liu et al., 2015). Thus, the identification of factors that can prevent abnormal VSMCs proliferation and migration could reveal novel therapeutic targets for vascular remodelling disorders.

Suramin, a hydrophilic polysulfonated naphthylurea, was originally used to treat African trypanosomiasis and onchocerciasis (Furtado et al., 2011; Kennedy, 2008). Clinical studies have shown that suramin is an effective anticancer agent that inhibits the proliferation of various tumour cells (Wang et al., 2018). Moreover, suramin acts at the exterior cell surface thus block the binding of various growth factors to their receptors, including platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and transforming growth factor-beta (TGF-β), thereby inhibiting cellular responses such as endothelial cells proliferation and migration (Little et al., 2013; Warn et al., 2001). In this study, we investigated the effects of suramin on VSMCs.

Transforming growth factor beta receptor 1 (TGFBR1) plays a vital role in the progression of cardiovascular diseases by regulating the proliferation, migration, and differentiation of VSMCs. TGFBR1 modulates the expression of target genes, such as CyclinD1, Proliferating Cell Nuclear Antigen (PCNA)by activating the Smad2/3 signalling pathway (Liu et al., 2011). VSMC-specific TGFBR1 deficiency suppressed arterial NIH (Liao et al., 2016). These results suggest that targeting TGFBR1 may be a potential therapeutic strategy for vascular remodelling disorders. Therefore, we hypothesised that suramin affects VSMCs by inhibiting growth factor-mediated growth in a Smad2/3-dependent manner. In this study, we used an in vitro platelet-derived growth factor type BB (PDGF-BB)-induced VSMCs proliferation and migration model and an in vivo left common carotid artery (LCCA) ligation model to investigate the ability of suramin to reduce vascular injury-induced NIH by suppressing the activation of the TGFBR1/Smad2/3 signalling pathway. Thus, suramin may be a potential treatment for NIH.