Statin therapy alone and in combination with an acyl-CoA:cholesterol O-acyltransferase inhibitor on experimental atherosclerosis.
Pathophysiol Haemost Thromb
; 36(1): 9-17, 2007.
Article
in En
| MEDLINE
| ID: mdl-18332609
ABSTRACT
The ability to modify the enzymatic processes involved in promoting atherosclerotic plaque disruption and to serially monitor atherosclerotic evolution could provide novel information in the management of patients with atherosclerosis. We studied the effects of a statin (atorvastatin) and its combination with an acyl-CoAcholesterol O-acyltransferase (ACAT) inhibitor (avasimibe) on atherosclerotic regression and plaque stability as measured by matrix metalloproteinase 1 and 3 (MMP-1 and MMP-3) levels. Watanabe Heritable Hyperlipidemic (WHHL) rabbits treated with atorvastatin alone experienced an attenuated increase in atherosclerotic burden versus controls as determined by MR imaging. The mean vessel wall area (VWA) prior to drug therapy was 5.57 +/- 0.01 mm2. The VWA increased to 6.71 +/- 0.03 and 7.16 +/- 0.03 mm2, respectively, in atorvastatin-treated and control groups (p < 0.0001 for both). The combination of atorvastatin and avasimibe induced a significant regression of the previously established atherosclerotic lesions, with the VWA decreasing to 4.54 +/- 0.04 mm2 (p = 0.009). Atorvastatin alone induced a nonsignificant reduction in the percent staining of MMP-1 in atherosclerotic lesions, but the combination treatment with avasimibe led to a significant reduction versus controls (p = 0.005). However, a reduction in MMP-3 staining was significant for rabbits treated with both atorvastatin alone (p = 0.007) and in combination with avasimibe (p = 0.04) versus controls. In this animal model, the addition of avasimibe to atorvastatin has beneficial effects on both atherosclerotic plaque regression and stabilization.
Full text:
1
Database:
MEDLINE
Main subject:
Aortic Diseases
/
Pyrroles
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Sulfonic Acids
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Sterol O-Acyltransferase
/
Hydroxymethylglutaryl-CoA Reductase Inhibitors
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Atherosclerosis
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Heptanoic Acids
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Hyperlipidemias
/
Acetates
Type of study:
Etiology_studies
Language:
En
Journal:
Pathophysiol Haemost Thromb
Year:
2007
Type:
Article
Affiliation country:
United States