Rosuvastatin Reduces Aortic Sinus and Coronary Artery Atherosclerosis in SR-B1 (Scavenger Receptor Class B Type 1)/ApoE (Apolipoprotein E) Double Knockout Mice Independently of Plasma Cholesterol Lowering

Arterioscler Thromb Vasc Biol. 2018 Jan;38(1):26-39. doi: 10.1161/ATVBAHA.117.305140. Epub 2017 Nov 21.


Objective: Rosuvastatin has been widely used in the primary and secondary prevention of coronary heart disease. However, its antiatherosclerotic properties have not been tested in a mouse model that could mimic human coronary heart disease. The present study was designed to test the effects of rosuvastatin on coronary artery atherosclerosis and myocardial fibrosis in SR-B1 (scavenger receptor class B type 1) and apoE (apolipoprotein E) double knockout mice.

Approach and results: Three-week-old SR-B1-/-/apoE-/- mice were injected daily with 10 mg/kg of rosuvastatin for 2 weeks. Compared with saline-treated mice, rosuvastatin-treated mice showed increased levels of hepatic PCSK9 (proprotein convertase subtilisin/kexin type-9) and LDLR (low-density lipoprotein receptor) message, increased plasma PCSK9 protein but decreased levels of hepatic LDLR protein and increased plasma total cholesterol associated with apoB (apolipoprotein B) 48-containing lipoproteins. In spite of this, rosuvastatin treatment was associated with decreased atherosclerosis in both the aortic sinus and coronary arteries and reduced platelet accumulation in atherosclerotic coronary arteries. Cardiac fibrosis and cardiomegaly were also attenuated in rosuvastatin-treated SR-B1-/-/apoE-/- mice. Two-week treatment with rosuvastatin resulted in significant decreases in markers of oxidized phospholipids in atherosclerotic plaques. In vitro analysis showed that incubation of bone marrow-derived macrophages with rosuvastatin substantially downregulated cluster of differentiation (CD)36 and inhibited oxidized LDL-induced foam cell formation.

Conclusions: Rosuvastatin protected SR-B1-/-/apoE-/- mice against atherosclerosis and platelet accumulation in coronary arteries and attenuated myocardial fibrosis and cardiomegaly, despite increased plasma total cholesterol. The ability of rosuvastatin to reduce oxidized phospholipids in atherosclerotic plaques and inhibit macrophage foam cell formation may have contributed to this protection.

Keywords: atherosclerosis; cholesterol; coronary artery disease; foam cells; macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aortic Diseases / genetics
  • Aortic Diseases / metabolism
  • Aortic Diseases / pathology
  • Aortic Diseases / prevention & control*
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Atherosclerosis / prevention & control*
  • Biomarkers / blood
  • Cells, Cultured
  • Cholesterol / blood*
  • Coronary Artery Disease / genetics
  • Coronary Artery Disease / metabolism
  • Coronary Artery Disease / pathology
  • Coronary Artery Disease / prevention & control*
  • Coronary Vessels / drug effects*
  • Coronary Vessels / metabolism
  • Coronary Vessels / pathology
  • Disease Models, Animal
  • Foam Cells / drug effects
  • Foam Cells / metabolism
  • Foam Cells / pathology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Lipoproteins, LDL / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Mice, Knockout, ApoE
  • Plaque, Atherosclerotic*
  • Proprotein Convertase 9 / metabolism
  • Receptors, LDL / metabolism
  • Rosuvastatin Calcium / pharmacology*
  • Scavenger Receptors, Class B / deficiency*
  • Scavenger Receptors, Class B / genetics
  • Sinus of Valsalva / drug effects*
  • Sinus of Valsalva / metabolism
  • Sinus of Valsalva / pathology


  • Biomarkers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipoproteins, LDL
  • Receptors, LDL
  • Scarb1 protein, mouse
  • Scavenger Receptors, Class B
  • oxidized low density lipoprotein
  • Rosuvastatin Calcium
  • Cholesterol
  • Pcsk9 protein, mouse
  • Proprotein Convertase 9