PDGF-stimulated smooth muscle cell behavior inhibited by decorin mimic

While the number of percutaneous coronary interventions (PCI) performed in the United States has increased by 33%, thrombosis, neointimal hyperplasia, and restenosis remain complications of this procedure and inhibit complete functional recovery of the vessel wall. While some progress has been made via the local delivery of anti-restenotic therapeutics from drug-eluting balloons and stents, the onset of thrombosis has left room for therapeutic improvement. Towards this effort, our laboratory has developed an antithrombotic therapeutic (DS-SILY) consisting of a dermatan sulfate backbone functionalized with collagen-binding peptides, which effectively inhibits collagen-induced platelet activation and encourages endothelial cell proliferation. Due to the negative charge associated with DS, DS-SILY binds to platelet derived growth factor (PDGF), in addition to other signaling molecules involved in the restenotic pathway, with high affinity. As such, PDGF-stimulated SMC cultures treated with DS-SILY demonstrate significantly decreased proliferation, migration, protein synthesis, and expression of inflammatory cytokines compared to cultures treated with PDGF alone. The trends demonstrated here correlate to responses exhibited intracellularly, where intracellular phosphorylation of the MAPKs ERK and p38 decreased with increased concentration of DS-SILY. These results indicate that the use of DS-SILY as an antithrombotic therapeutic during PCI could aid in the functional healing of the injured vessel wall.