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Statins and nitric oxide donors affect thrombospondin 1-induced chemotaxis

Keri Seymour1, Jeffrey Stein1, Xuan Han1

  • 1Division 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.

Vascular and Endovascular Surgery
|November 2, 2014
PubMed

Insights

Short-term statin use inhibits vascular smooth muscle cell migration induced by thrombospondin 1. However, nitric oxide donors can reverse this statin effect, indicating potential for combination therapies.

Area of Science:

  • Cardiovascular Biology
  • Pharmacology
  • Cellular Biology

Background:

  • Thrombospondin 1 (TSP-1) is implicated in vascular smooth muscle cell (VSMC) migration and intimal hyperplasia.
  • Statins and nitric oxide (NO) donors are known to reduce intimal hyperplasia.
  • Previous research indicated that statins and NO donors inhibit TSP-1-induced VSMC chemotaxis.

Purpose of the Study:

  • To investigate if short-term statin pretreatment inhibits TSP-1-induced VSMC chemotaxis.
  • To determine if NO donors enhance statin inhibition of TSP-1- or platelet-derived growth factor (PDGF)-induced VSMC chemotaxis.

Main Methods:

  • Examined the effects of long-term (20 hours) versus short-term (20 minutes) pravastatin on TSP-1-induced VSMC chemotaxis.
  • Assessed the impact of diethylenetriamine NONOate (DETA/NO) or S-nitroso-N-acetylpenicillamine (SNAP) in combination with pravastatin.
  • Compared TSP-1 with PDGF as chemoattractants in the presence of DETA/NO and pravastatin.

Main Results:

  • Both long-term and short-term pravastatin inhibited TSP-1-induced VSMC chemotaxis.
  • DETA/NO and SNAP diminished the inhibitory effect of statins on TSP-1-induced chemotaxis.
  • PDGF and TSP-1 exhibited opposing effects when used with DETA/NO and pravastatin.

Conclusions:

  • Short-term statin pretreatment demonstrates a pleiotropic effect by inhibiting TSP-1-induced VSMC chemotaxis.
  • High-dose NO reversed statin-mediated inhibition of TSP-1-induced chemotaxis.
  • The interplay between NO and statins suggests combination therapies warrant further investigation for cardiovascular applications.
Abstract

Keywords:
migrationnitric oxidestatinsthrombospondinvascular smooth muscle cells

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