Statins and nitric oxide donors affect thrombospondin 1-induced chemotaxis

  • Vasc Endovascular Surg. 2014 Oct-Nov;48(7-8):470-5. doi: 10.1177/1538574414554718.
Keri Seymour  1 ,  Jeffrey Stein  1 ,  Xuan Han  1 ,  Kristopher G Maier  1 ,  Vivian Gahtan  2
Affiliations
  • 1. Division of Vascular Surgery and Endovascular Services, SUNY Upstate Medical University, Syracuse, NY, USA Department of Veterans Affairs, VA Healthcare Network Upstate New York at Syracuse, Syracuse, NY, USA.
  • 2. Division of Vascular Surgery and Endovascular Services, SUNY Upstate Medical University, Syracuse, NY, USA Department of Veterans Affairs, VA Healthcare Network Upstate New York at Syracuse, Syracuse, NY, USA [email protected].
PMID: 25361959 DOI: 10.1177/1538574414554718
Abstract

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.

Keywords
migration; nitric oxide; statins; thrombospondin; vascular smooth muscle cells.
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