Abstract | BACKGROUND: METHODS AND RESULTS:
ApoE-deficient mice were maintained for 17 weeks on a Western-type diet without (control) or with the ACAT inhibitor F-1394 (effective against ACAT1 and ACAT2) at doses of either 300 (low) or 900 (high) mg/kg. Intimal lesion area at the aortic sinus in controls was 0.69+/-0.06 mm(2). F-1394 treatment significantly decreased lesional area by 39% (low) or 45% (high). F-1394 treatment also reduced lesional immunostaining for macrophages by 61% (low) or 83% (high). En face analysis showed that surface lipid staining in control aortas was 20.0+/-2.8%; F-1394 treatment reduced this by 46% (low) or 62% (high). There were no obvious signs of systemic or vessel wall toxicity associated with F-1394 treatment. CONCLUSIONS: Partial ACAT inhibition by F-1394 had antiatherogenic effects in apoE-deficient mice that were achieved without obvious toxicity. Partial ACAT inhibition may have therapeutic potential in the clinical treatment of atherosclerosis.
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Authors | J Kusunoki, D K Hansoty, K Aragane, J T Fallon, J J Badimon, E A Fisher |
Journal | Circulation
(Circulation)
Vol. 103
Issue 21
Pg. 2604-9
(May 29 2001)
ISSN: 1524-4539 [Electronic] United States |
PMID | 11382731
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Apolipoproteins E
- Cyclohexanes
- Dioxanes
- Enzyme Inhibitors
- F 1394
- Cholesterol
- Sterol O-Acyltransferase
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Topics |
- Animals
- Aorta
(drug effects, metabolism)
- Apolipoproteins E
(deficiency, genetics)
- Arteriosclerosis
(enzymology, pathology, prevention & control)
- Body Weight
(drug effects)
- Cholesterol
(blood)
- Cyclohexanes
(pharmacology)
- Dioxanes
(pharmacology)
- Enzyme Inhibitors
(pharmacology)
- Female
- Linear Models
- Lipid Metabolism
- Macrophages
(drug effects, metabolism)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Sterol O-Acyltransferase
(antagonists & inhibitors, metabolism)
- Tunica Intima
(drug effects, pathology)
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