NK-104, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, reduces osteopontin expression by rat aortic smooth muscle cells

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.