title: Decorin mimic inhibits vascular smooth muscle proliferation and migration.
abstract: Over the past 10 years, the number of percutaneous coronary intervention procedures performed in the United States increased by 33%; however, restenosis, which inhibits complete functional recovery of the vessel wall, complicates this procedure. A wide range of anti-restenotic therapeutics have been developed, although many elicit non-specific effects that compromise vessel healing. Drawing inspiration from biologically-relevant molecules, our lab developed a mimic of the natural proteoglycan decorin, termed DS-SILY, which can mask exposed collagen and thereby effectively decrease platelet activation, thus contributing to suppression of vascular intimal hyperplasia. Here, we characterize the effects of DS-SILY on both proliferative and quiescent human SMCs to evaluate the potential impact of DS-SILY-SMC interaction on restenosis, and further characterize in vivo platelet interactions. DS-SILY decreased proliferative SMC proliferation and pro-inflammatory cytokine secretion in vitro in a concentration dependent manner as compared to untreated controls. The addition of DS-SILY to in vitro SMC cultures decreased SMC migration and protein synthesis by 95% and 37%, respectively. Furthermore, DS-SILY decreased platelet activation, as well as reduced neointimal hyperplasia by 60%, in vivo using Ossabaw swine. These results indicate that DS-SILY demonstrates multiple biological activities that may all synergistically contribute to an improved treatment paradigm for balloon angioplasty.
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, United States of America.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Scott
authors.forename: John E
authors.initials: JE
authors.lastname: Paderi
authors.forename: Michael
authors.initials: M
authors.lastname: Sturek
authors.forename: Alyssa
authors.initials: A
authors.lastname: Panitch
mesh_terms: D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D058575:Decorin / Q000502:physiology*; D006801:Humans; D018716:Molecular Mimicry; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D015539:Platelet Activation; D018180:Thrombomodulin / Q000378:metabolism; D017539:Tunica Intima / Q000166:cytology
chemical_list: C546878:DCN protein, human; D058575:Decorin; D018180:Thrombomodulin