YC-1-mediated vascular protection through inhibition of smooth muscle cell proliferation and platelet function.

Published

Journal Article

YC-1, a synthetic benzyl indazole derivative, is capable of stimulating endogenous vessel wall cyclic guanosine monophosphate (cGMP) production and attenuating the remodeling response to experimental arterial angioplasty. In an effort to investigate the mechanisms of this YC-1-mediated vasoprotection, we examined the influence of soluble YC-1 or YC-1 incorporated in a polyethylene glycol (PEG) hydrogel on cultured rat vascular smooth muscle cell (SMC) cGMP synthesis, SMC proliferation, and platelet function. Results demonstrate that soluble YC-1 stimulated SMC cGMP production in a dose-dependent fashion, while both soluble and hydrogel-released YC-1 inhibited vascular SMC proliferation in a dose-dependent fashion without effects on cell viability. Platelet aggregation and adherence to collagen were both significantly inhibited in a dose-dependent fashion by soluble and hydrogel-released YC-1. Arterial neointima formation following experimental balloon injury was significantly attenuated by perivascular hydrogel-released YC-1. These results suggest that YC-1 is a potent, physiologically active agent with major anti-proliferative and anti-platelet properties that may provide protection against vascular injury through cGMP-dependent mechanisms.

Full Text

Duke Authors

Cited Authors

  • Tulis, DA; Bohl Masters, KS; Lipke, EA; Schiesser, RL; Evans, AJ; Peyton, KJ; Durante, W; West, JL; Schafer, AI

Published Date

  • March 2002

Published In

Volume / Issue

  • 291 / 4

Start / End Page

  • 1014 - 1021

PubMed ID

  • 11866467

Pubmed Central ID

  • 11866467

Electronic International Standard Serial Number (EISSN)

  • 1090-2104

International Standard Serial Number (ISSN)

  • 0006-291X

Digital Object Identifier (DOI)

  • 10.1006/bbrc.2002.6552

Language

  • eng