Article date: May 2001
By: Minoru Takemoto, Masaki Kitahara, Koutaro Yokote, Sunao Asaumi, Ayako Take, Yasushi Saito, Seijiro Mori in Volume 133, Issue 1, pages 83-88
It has been suggested that osteopontin promotes the development of atherosclerosis, especially under diabetic conditions.
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.
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.
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.
These data support a notion that NK‐104 is a suitable drug for the treatment of diabetic patients with hypercholesterolaemia.
It has been suggested that osteopontin promotes the development of atherosclerosis, especially under diabetic conditions.
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.
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.
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.
These data support a notion that NK‐104 is a suitable drug for the treatment of diabetic patients with hypercholesterolaemia.
British Journal of Pharmacology (2001) 133, 83–88; doi:10.1038/sj.bjp.0704046
DOI: 10.1038/sj.bjp.0704046
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