Inhibition of smooth muscle cell proliferation and intimal thickening with small peptide mimetics of soluble N-cadherin

Cressida Lyon, Sandra Medina Villar, Imke Sittel, Alexandra Wasmuth, Carmen Galan, Sarah George

Research output: Chapter in Book/Report/Conference proceedingConference Contribution (Conference Proceeding)

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Abstract

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.
Original languageEnglish
Title of host publication85th European Atherosclerosis Society Congress
Subtitle of host publicationCongress Abstracts Presentations
PublisherEuropean Atherosclerosis Society/International Atherosclerosis Society
Pagese64-e65
Number of pages1
DOIs
Publication statusPublished - Aug 2017

Publication series

NameAtherosclerosis
PublisherElsevier
NumberSuppl C
Volume263
ISSN (Print)0021-9150

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