Abstract 4490: The Wnt Agonist, SKL2020 Inhibits Neointimal Hyperplasia but Facilitates Re-Endothelialization, When Treated with Rapamycin in Porcine Coronary Artery Stent Model
Recent studies suggested that Drug-eluting stent (DES) is associated with increased risk of late stent thrombosis (LST). Even though the mechanism of LST is still not clear, poor re-endothelialization by anti-proliferative agents released from DES is considered to be one of the major reasons. Meanwhile, it has been reported that Wnt/β-catenin signaling plays a crucial role in survival of endothelial cells. We screened SKL2020 as a Wnt/β-catenin agonist, that was proved to be a new endothelial cell (EC) specific proliferative agent. SKL2020 enhanced EC proliferation without affecting vascular smooth muscle cell (VSMC) proliferation in vitro test. For pig coronary stent model, 3 coronary arteries randomly selected for the implantation of polymer(PLGA)-only stent, rapamycin-eluting stent (180μg/stent), and the combination of Rapamycin (180μg/stent) and SKL2020(45, 90, 180μg/stent) eluting stents (n=8 per each group). The quantitative pathological analysis was performed blinded to groups after 4 weeks. The re-endothelialization was significantly increased in the combination group (84±6.8%, p=0.013 vs rapamycin) compared to the rapamycin group (67.9±11.2%) and polymer only group (80.2±8.7%). The neo-intimal area was significantly smaller in the combination group (1.1±0.3 mm2, p=0.007 vs polymer) compared to polymer group (2.7±0.7 mm2) and rapamycin group (1.8±0.3%, p=0.005 vs polymer). When combined with rapamycin, the SKL2020 facilitated EC proliferation and inhibited neointimal proliferation both in vitro and in vivo study, suggesting it may be an ideal agent for DES preventing both restenosis and stent thrombosis.