Aim: We investigated whether a small peptide sequence from soluble Ncadherin (SNC) modulated intimal thickening by changing vascular smooth muscle cell (VSMC),fibroblast and endothelial cell (EC) behaviour. Restenosis of vein grafts is a significant problem resulting in failure in 30-50% of patients. Reduction of VSMC proliferation, without preventing re-endothelialisation is desirable. SNC reduced ex vivo intimal thickening and increased endothelial coverage. We wish to produce a smaller therapeutic peptide. Methods: Cells: Human saphenous vein VSMC and fibroblasts; HUVECs. Proliferation: EdU incorporation. Migration: scratch wound assay (distance migrated, mm). Apoptosis: cleaved caspase-3 immunocytochemistry. Human saphenous vein organ culture used as ex vivo model of intimal thickening, analysed by elastin van Gieson staining (intimal size), EdU (proliferation) and Q-Bend-10 (endothelial coverage). Results: The peptide significantly reduced VSMC proliferation (14.4±4.8% vs 3.58±2.2%, n¼4, p<0.05). Conclusions: A peptide mimetic of SNC is an attractive therapeutic for restenosis as it attenuates VSMC proliferation, without detrimental effects on re-endothelialisation. A peptide is inexpensive to produce and easy to deliver.