BACKGROUND Studies in dogs showed that some hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) are associated with cataract when administered in excessive doses. Clinical safety data of statins regarding cataract development in humans have been of limited value so far. OBJECTIVE To determine whether long-term use of statins is associated with an increased risk of cataract. METH...

We did a secondary analysis of data from three large colorectal adenoma chemoprevention trials to assess the association between 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor use and reduced risk of recurrent colorectal adenomas. Reported use of HMG-CoA reductase inhibitors was not associated with a reduced recurrence of colorectal adenomas, multiple adenomas, or advanced ...

BACKGROUND: Surrogate measures for cardiovascular disease events have the potential to increase greatly the efficiency of clinical trials. A leading candidate for such a surrogate is the progression of intima-media thickness (IMT) of the carotid artery; much experience has been gained with this endpoint in trials of HMG-CoA reductase inhibitors (statins). METHODS AND RESULTS: We examine two sep...

BACKGROUND Many trials have shown that 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors reduce the incidence of cardiovascular events and mortality. One method of decreasing the incidence of cardiovascular events could be to reduce the progression of coronary atherosclerosis, and a recent study found that atorvastatin can cause coronary plaque to regress. To generalize this...

BACKGROUND Alterations in the mevalonate pathway may contribute to malignant cell growth. There are differences in the aetiology, clinical behaviour, pathological and genetic features in cancer of the right versus the left colon. Here, 3-hydroxy-3-methylglutatyl coenzyme A (HMG-CoA) reductase, farnesylpyrophosphate (FPP) synthase and farnesyltransferase (Ftase) activities were measured in human...

A somatic cell mutant of the CHO-K1 cell selected to be resistant to the killing effects of 25-hydroxycholesterol in the absence of cholesterol is shown to be defective in the inhibition of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity by 25-hydroxycholesterol, cholesterol, and lipoproteins, thus maintaining the enzyme activity found in cells in the absence of exogenous sterol con...

According to traditional thinking, atherosclerosis results from passive lipid deposition in the vascular wall. Thus, therapies predominantly targeted lipid metabolism. The contemporary view of atherosclerosis, however, has broadened to include an active and complex role for inflammation, orchestrated in part by mediators of the immune system. This recognition prompted the question of whether an...

In familial hypercholesterolemia (FH), the efficacy of the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase shows considerable interindividual variation, and several genetic and environmental factors can contribute to explaining this variability. A randomized, double-blind, placebo-controlled clinical trial with simvastatin, an HMG-CoA reductase inhibitor, was conducted i...

The two compounds compactin and ML-236B are identical fungal metabolites isolated from strains of Penicilliunz brevicompactum and Penicillium citrinum, respectively. ML-236B has been shown to be a potent competitive inhibitor of rat liver microsomal 3-hydroxy-3-methylgluiaryl coenzyme A reductase (HMG-CoA reductase), the rate-controlling enzyme in cholesterol biosynthesis (Endo, A., Kuroda, M.,...

The mechanism by which competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase decrease serum cholesterol is incompletely understood. The few available data in humans suggest that chronic administration of the competitive inhibitor, lovastatin, decreases serum cholesterol with little or no change in total body sterol synthesis. To further define the effect of lovasta...