Rosuvastatin reduces atherosclerosis development beyond and independent of its plasma cholesterol-lowering effect in APOE3-Leiden transgenic mice: Evidence for antiinflammatory effects of rosuvastatin

Statins can exert anti-inflammatory antiatherosclerotic effects through an anti-inflammatory action, independent of lowering cholesterol. We addressed the question whether the anti-inflammatory activities of statins can reduce atherosclerosis beyond the reduction achieved by cholesterol lowering per...

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Published in:Circulation (New York, N.Y.) N.Y.), 2003-09, Vol.108 (11), p.1368-1374
Main Authors: KLEEMANN, Robert, PRINCEN, Hans M. G, EMEIS, Jef J, JUKEMA, J. Wouter, FONTIJN, Ruud D, HORREVOETS, Anton J. G, KOOISTRA, Teake, HAVEKES, Louis M
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents - therapeutic use
Aorta - drug effects
Aorta - metabolism
Aorta - pathology
Apolipoprotein E3
Apolipoproteins E - genetics
Arteriosclerosis - blood
Arteriosclerosis - drug therapy
Arteriosclerosis - immunology
Arteriosclerosis - pathology
Biological and medical sciences
Cell Adhesion
Cholesterol - blood
Cytokines - metabolism
Female
Fluorobenzenes - therapeutic use
General and cellular metabolism. Vitamins
Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use
Lipids - blood
Lipoproteins - blood
Macrophages - immunology
Medical sciences
Mice
Mice, Transgenic
Monocytes - immunology
Pharmacology. Drug treatments
Pyrimidines
Rosuvastatin Calcium
Sulfonamides
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Summary:Statins can exert anti-inflammatory antiatherosclerotic effects through an anti-inflammatory action, independent of lowering cholesterol. We addressed the question whether the anti-inflammatory activities of statins can reduce atherosclerosis beyond the reduction achieved by cholesterol lowering per se. Two groups of 20 female APOE*3-Leiden mice received either a high-cholesterol diet (HC) or a high-cholesterol diet supplemented with 0.005% (wt/wt) rosuvastatin (HC+R). The HC diet alone resulted in a plasma cholesterol concentration of 18.9+/-1.4 mmol/L, and administration of rosuvastatin lowered plasma cholesterol to 14.1+/-0.7 mmol/L. In a separate low-cholesterol (LC) control group, the dietary cholesterol intake was reduced, which resulted in plasma cholesterol levels that were comparable to the HC+R group (13.4+/-0.8 mmol/L). Atherosclerosis in the aortic root area was quantified after 24 weeks. As compared with the HC group, the LC group had a 62% (P
ISSN:0009-7322
1524-4539
DOI:10.1161/01.CIR.0000086460.55494.AF