Differential effect of nitric oxide on thrombospondin-1-, PDGF- and fibronectin-induced migration of vascular smooth muscle cells.
BACKGROUND: Neointimal hyperplasia involves the migration of medial vascular smooth muscle cells (VSMCs) in response to arterial injury. Thrombospondin-1 (TSP1), platelet-derived growth factor (PDGF), and fibronectin (Fn) induce VSMC migration. Nitric oxide (NO) limits VSMC migration. The hypothesis of this study is that NO would dose dependently inhibit TSP1-induced, PDGF-induced, and Fn-induced VSMC chemotaxis. METHODS: VSMCs were pretreated with serum free media or the NO donors diethylenetriamine NONOate or S-nitroso-N-acetyl-D,L-penicillamine. Chemotaxis to TSP1, PDGF, or Fn was determined. Analysis of variance with post hoc testing was done. P values < .05 were considered significant. RESULTS: PDGF, TSP1, and Fn induced VSMC chemotaxis. NO donors inhibited chemotaxis of VSMCs to PDGF in a concentration-dependent manner. NO donors had a variable effect on TSP1-induced chemotaxis. NO donors did not inhibit Fn-induced chemotaxis. CONCLUSION: The complex interactions of these proteins in vivo will need to be considered when developing NO-dependent therapies for neointimal hyperplasia.
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- Thrombospondin 1
- Surgery
- Signal Transduction
- Platelet-Derived Growth Factor
- Nitric Oxide
- Muscle, Smooth, Vascular
- Humans
- Fibronectins
- Cells, Cultured
- Cell Proliferation
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Thrombospondin 1
- Surgery
- Signal Transduction
- Platelet-Derived Growth Factor
- Nitric Oxide
- Muscle, Smooth, Vascular
- Humans
- Fibronectins
- Cells, Cultured
- Cell Proliferation