title: Decorin mimic promotes endothelial cell health in endothelial monolayers and endothelial-smooth muscle co-cultures.
abstract: Non-specific cytotoxins, including paclitaxel and sirolimus analogues, currently utilized as anti-restenotic therapeutics, affect not only smooth muscle cells (SMCs) but also neighbouring vascular endothelial cells (ECs). These drugs inhibit the formation of an intact endothelium following vessel injury, thus emphasizing the critical need for new candidate therapeutics. Utilizing our in vitro models, including EC monolayers and both hyperplastic and quiescent EC-SMC co-cultures, we investigated the ability of DS-SILY20, a decorin mimic, to promote EC health. DS-SILY20increased EC proliferation and migration by 1.5- and 2-fold, respectively, which corresponded to increased phosphorylation of ERK-1/2. Interestingly, IL-6 secretion and the production of both E-selectin and P-selectin were reduced in the presence of 10 μm DS-SILY20, even in the presence of the potent pro-inflammatory cytokine platelet-derived growth factor (PDGF). In hyperplastic and quiescent EC-SMC co-cultures, DS-SILY20treatment reduced the secretion of IFNγ, IL-1β, IL-6 and TNFα, corresponding to a 23% decrease in p38 phosphorylation. E-selectin and P-selectin expression was further reduced following DS-SILY20treatment in both co-culture models. These results indicate that DS-SILY20promotes EC health and that this decorin mimic could serve as a potential therapeutic to promote vessel healing following percutaneous coronary intervention (PCI). Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Scott
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.
authors.forename: Aneesh K
authors.initials: AK
authors.lastname: Ramaswamy
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.|School of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN, USA.
authors.forename: Kinam
authors.initials: K
authors.lastname: Park
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Panitch
mesh_terms: D040761:Biomimetic Materials / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D058575:Decorin; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*
chemical_list: D016207:Cytokines; C546878:DCN protein, human; D058575:Decorin; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: co-culture; decorin; dermatan sulphate; endothelial cells; proteoglycan; vascular smooth muscle cells