Statins and nitric oxide donors affect thrombospondin 1-induced chemotaxis.

Journal Article (Journal Article)

BACKGROUND: Thrombospondin 1 (TSP-1) induces vascular smooth muscle cell (VSMC) migration and intimal hyperplasia. Statins and nitric oxide (NO) donors decrease intimal hyperplasia. We previously showed that statins (long-term exposure) and NO donors inhibit TSP-1-induced VSMC chemotaxis. HYPOTHESES: (1) Pretreatment with short-term statin will inhibit TSP-1-induced VSMC chemotaxis and (2) NO donors will enhance statin inhibition of TSP-1-induced or platelet-derived growth factor (PDGF)-induced VSMC chemotaxis. METHODS: We examined these treatment effects on TSP-1-induced VSMC chemotaxis: (1) long-term (20 hours) versus short-term (20 minutes) pravastatin, (2) diethylenetriamine NONOate (DETA/NO) or S-nitroso-N-acetylpenicillamine (SNAP) in combination with pravastatin, and (3) comparison of TSP-1 to PDGF as a chemoattractant. RESULTS: Pravastatin (long term or short term) inhibited TSP-1-induced chemotaxis. Diethylenetriamine NONOate and SNAP impeded statin inhibition of TSP-1-induced chemotaxis. Platelet-derived growth factor and TSP-1 had opposite effects on DETA/NO-pravastatin treatment. CONCLUSION: Short-term statin pretreatment inhibited TSP-1-induced VSMC chemotaxis, suggesting a pleiotropic effect. High-dose NO reversed statin inhibition of TSP-1-induced chemotaxis, suggesting NO and statin combination therapies warrant further study.

Full Text

Duke Authors

Cited Authors

  • Seymour, K; Stein, J; Han, X; Maier, KG; Gahtan, V

Published Date

  • October 2014

Published In

Volume / Issue

  • 48 / 7-8

Start / End Page

  • 470 - 475

PubMed ID

  • 25361959

Electronic International Standard Serial Number (EISSN)

  • 1938-9116

Digital Object Identifier (DOI)

  • 10.1177/1538574414554718


  • eng

Conference Location

  • United States