Scutellarin-eluting stents attenuate coronary restenosis by inhibiting the abnormal proliferation and migration of vascular smooth muscle cells through suppression of NF-κB signaling.

BACKGROUND: Coronary restenosis remains a major challenge following percutaneous coronary intervention (PCI), necessitating the development of effective stent-eluting drugs. Previous studies indicate that scutellarin protects vascular endothelial cells and exhibits anti-thrombotic and anti-platelet effects. Notably, our prior research demonstrated that scutellarin specifically counteracts oxidative stress-driven endothelial dysfunction, a key initiating event in restenosis. This combined evidence strongly suggests its potential against in-stent restenosis (ISR). Therefore, this study explores the efficacy of scutellarin in preventing ISR after PCI.

PURPOSE: We investigated scutellarin, derived from Erigeron breviscapus, for its potential to prevent ISR following PCI.

STUDY DESIGN: The efficacy and mechanism of scutellarin were evaluated using both in vivo and in vitro models.

METHODS: An experimental atherosclerosis model was established in APOE-/- mice. A coronary stenosis stent model was subsequently developed in minipigs through high-fat diet and balloon induced injury. Scutellarin-eluting stents with varying doses were implanted at stenosis sites. At 28 days post-PCI, multimodal imaging (QCA, OCT, IVUS) was performed to assess anti-restenosis efficacy. Additionally, in vitro H2O2-induced vascular smooth muscle cells (VSMCs) were used to monitor proliferation and migration. Protein levels were measured to elucidate molecular mechanisms.

RESULTS: In APOE-/- mice, scutellarin significantly reduced lipid deposition in aortic plaques and suppressed inflammatory responses. In the porcine model, it markedly decreased neointimal thickness, neointimal area, and restenosis rates, while inhibiting inflammation. Collectively, these two in vivo models demonstrate that scutellarin-eluting stents effectively inhibit ISR. In vitro, scutellarin suppressed VSMCs proliferation and migration and mediated a shift from necrosis to autophagy-coordinated apoptosis. Mechanistically, scutellarin-mediated suppression of the synthetic phenotype switch in VSMCs was accompanied by the coordinated downregulation of both the Pl3K/AKT and IKKs/NF-κB cascades.

CONCLUSIONS: This study establishes the efficacy of scutellarin in mitigating ISR using two complementary in vivo models. Scutellarin-eluting stents in atherosclerotic minipigs overcome translational barriers through full interventional simulation. Furthermore, scutellarin inhibits VSMCs proliferation, migration and promotes autophagy-coordinated apoptosis by the coordinated downregulation of both the Pl3K/AKT and lKKs/NF-κB cascades.These findings highlight scutellarin as a promising candidate for next-generation bioactive stent coatings, bridging phytopharmacology and precision interventional cardiology.