Nstpbp5185, a novel benzimidazole derivative, suppresses PDGF signaling and reduces neointimal hyperplasia following vascular injury

Restenosis remains a significant clinical challenge following percutaneous coronary interventions such as angioplasty and stenting. Despite advances in techniques and drug-eluting stents, neointimal hyperplasia and vessel re-narrowing still occur in many patients. Platelet-derived growth factor (PDGF) plays a crucial role in restenosis by promoting the migration and proliferation of vascular smooth muscle cells (VSMCs). We previously demonstrated that nstpbp5185, an orally bioavailable thromboxane A₂ receptor (TP receptor) antagonist, exhibits anti-platelet, anti-thrombotic, and anti-atherosclerotic effects in murine models. In this study, we investigated whether nstpbp5185 could attenuate restenosis after vascular injury. In vitro, nstpbp5185 dose-dependently inhibited PDGF-stimulated VSMC migration and proliferation, reduced phosphorylation of PDGF receptor and downstream signaling molecules, and markedly suppressed PDGF-induced reactive oxygen species production. In vivo, nstpbp5185 significantly reduced neointimal formation and plasma levels of thromboxane B₂ in a rat carotid artery balloon injury model. Furthermore, nstpbp5185 suppressed VSMC proliferation in response to U46619, a TP receptor agonist, and inhibited U46619-induced platelet aggregation in platelet-rich plasma from treated rats. These findings suggest that nstpbp5185 effectively reduces restenosis by inhibiting PDGF signaling and antagonizing the TXA2-mediated response, supporting its potential as a therapeutic candidate for preventing restenosis after coronary intervention.