Rosuvastatin reduced deep vein thrombosis in ApoE gene deleted mice with hyperlipidemia through non-lipid lowering effects

Thromb Res. 2013 Mar;131(3):268-76. doi: 10.1016/j.thromres.2012.12.006. Epub 2012 Dec 29.

Abstract

Introduction: Statins, particularly rosuvastatin, have recently become relevant in the setting of venous thrombosis. The objective of this study was to study the non-lipid lowering effects of rosuvastatin in venous thrombosis in mice with hyperlipidemia.

Materials and methods: An inferior vena cava ligation model of venous thrombosis in mice was utilized. Saline or 5mg/kg of rosuvastatin was administered by gavage 48hs previous to thrombosis. Blood, the inferior vena cava, thrombus, and liver were harvested 3, 6hours, and 2days post-thrombosis. Thrombus weight, inflammatory markers, and plasminogen activator inhibitor-1 expression and plasma levels were measured. Also, neutrophil migration to the IVC was assessed.

Results: Rosuvastatin significantly decreased thrombus weight, plasminogen activator inhibitor-1 expression and plasma levels, expression of molecules related to the interleukin-6 pathway, and neutrophil migration into the vein wall.

Conclusions: This work supports the beneficial effects of rosuvastatin on venous thrombosis in mice with hyperlipidemia, due to its non-lipid lowering effects.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / genetics
  • Cell Movement
  • Disease Models, Animal
  • Fluorobenzenes / pharmacology*
  • Gene Deletion
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hyperlipidemias / drug therapy*
  • Hyperlipidemias / genetics
  • Inflammation / pathology
  • Interleukin-6 / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Neutrophils / cytology
  • Neutrophils / metabolism
  • P-Selectin / metabolism
  • Pyrimidines / pharmacology*
  • Rosuvastatin Calcium
  • Serpin E2 / metabolism
  • Sulfonamides / pharmacology*
  • Thrombosis / pathology
  • Time Factors
  • Vena Cava, Inferior / surgery
  • Venous Thrombosis / drug therapy*

Substances

  • Apolipoproteins E
  • Fluorobenzenes
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Interleukin-6
  • P-Selectin
  • Pyrimidines
  • Serpin E2
  • Serpine2 protein, mouse
  • Sulfonamides
  • Rosuvastatin Calcium