Incubating Hep G2 cells for 18 h with triparanol, buthiobate and low concentrations (less than 0.5 microM) of U18666A, inhibitors of desmosterol delta 24-reductase, of lanosterol 14 alpha-demethylase and of squalene-2,3-epoxide cyclase (EC 5.4.99.7) respectively, resulted in a decrease of the HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase activity. However, U18666A at concentrations ...

Hyperhomocysteinemia, an elevation of blood homocysteine levels, is a metabolic disorder associated with dysfunction of multiple organs. We previously demonstrated that hyperhomocysteinemia stimulated hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase leading to hepatic lipid accumulation and liver injury. The liver plays an important role in cholesterol biosynthesis and overall ...

3-hydroxy-3-methyl-glutaryl CoA (HMG-CoA) reductase inhibitors or statins are competitive inhibitors of the rate-limiting enzyme in cholesterol biosynthesis. Several large landmark clinical studies have shown a marked reduction of cardiovascular mortality and morbidity in patients treated with statins. Because of the strong association between serum cholesterol levels and coronary artery diseas...

CONTEXT Recent animal studies have suggested that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) increase bone formation, volume, and density. It is unknown whether use of statins is associated with a decreased risk of fractures in humans. OBJECTIVE To determine whether exposure to statins, fibrates, or other lipid-lowering drugs is associated with reduced bone...

Four drugs that act as specific inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase--lovastatin, pravastatin, simvastatin, and, most recently, fluvastatin--have been approved by regulatory authorities throughout the world. In the present review, we have critically assessed the comparative hypocholesterolemic effects of these four drugs based on direct comparative studies, wh...

Inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, such as simvastatin, lower circulating cholesterol levels and prevent myocardial infarction. Several studies have shown an unexpected effect of HMG-CoA reductase inhibitors on inflammation. Here, we confirm that simvastatin is anti-inflammatory by using a classic model of inflammation: carrageenan-induced foot pad edema. Simvast...

Apomine, a 1,1-bisphosphonate-ester with antitumor activity, has previously been reported to strongly down-regulate 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), the rate-limiting enzyme in the mevalonate pathway responsible for the prenylation of proteins. Here, we show that although apomine down-regulated HMG-CoA reductase protein levels in myeloma cells, it did not inh...

M any people have high blood cholesterol that may lead to coronary heart disease (CHD). A multifaceted approach consisting of diet, exercise, and pharmacological management is recommended to lower the risk of CHD.1 Elevated low-density lipoprotein-cholesterol (LDL-C) has been established as a major cause of CHD.1 The group of cholesterol-lowering drugs known as statins (3-hydroxy3-methylglutary...

BACKGROUND AND PURPOSE Statins reduce the risk of stroke recurrence, but the benefits of statins in improving outcome of acute stroke patients have not been well explored. METHODS We assessed potential effects of statins initiated before or within 4 weeks of stroke on 90-day outcome. Favorable outcomes were National Institutes of Health Stroke Scale (NIHSS) score < or =2 at 12 weeks and modif...

-Macrophages secrete matrix metalloproteinases (MMPs) that may weaken the fibrous cap of atherosclerotic plaque, predisposing its fissuration. The 92-kDa gelatinase B (MMP-9) has been identified in abdominal aortic aneurysms and in atherosclerotic tissues. Fluvastatin, through the inhibition of the isoprenoid pathway, inhibits major processes of atherogenesis in experimental models (smooth musc...