Abstract
1. It has been suggested that osteopontin promotes the development of atherosclerosis, especially under diabetic conditions. 2. In the present study, we found that NK-104, a new potent synthetic inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, reduced osteopontin expression both at protein and mRNA levels in cultured rat aortic smooth muscle cells. 3. The inhibitory effect of NK-104 was almost completely reversed by mevalonate, suggesting that mevalonate or its metabolites play important roles in the regulation of osteopontin expression. 4. Furthermore, oral administration of NK-104 (3 mg kg(-1) day(-1) for 7 days) effectively suppressed abnormally upregulated expression of osteopontin mRNA in the aorta and kidney of streptozotocin-induced diabetic rats. 5. These data support a notion that NK-104 is a suitable drug for the treatment of diabetic patients with hypercholesterolaemia.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Animals
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Aorta / cytology
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Aorta / drug effects*
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Aorta / metabolism
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Blotting, Western
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Cells, Cultured
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Diabetes Mellitus, Experimental / drug therapy
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Diabetes Mellitus, Experimental / genetics
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Diabetes Mellitus, Experimental / metabolism
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Gene Expression Regulation / drug effects*
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
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Kidney / drug effects
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Kidney / metabolism
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Male
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Mevalonic Acid / pharmacology
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Muscle, Smooth, Vascular / cytology
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Muscle, Smooth, Vascular / drug effects*
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Muscle, Smooth, Vascular / metabolism
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Osteopontin
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Quinolines / administration & dosage
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Quinolines / antagonists & inhibitors
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Quinolines / pharmacology*
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Quinolines / therapeutic use
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Rats, Wistar
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Sialoglycoproteins / biosynthesis
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Sialoglycoproteins / genetics*
Substances
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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Quinolines
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RNA, Messenger
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Sialoglycoproteins
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Spp1 protein, rat
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Osteopontin
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pitavastatin
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Mevalonic Acid