PURPOSE OF REVIEW To discuss unresolved issues and recent findings regarding the use of statins in heart failure. RECENT FINDINGS Recent data from Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico--Heart Failure and Controlled Rosuvastatin Multinational Trial in Heart Failure suggest that statins did not have any effect on outcome despite significant reduction in low-d...

Because the small bowel is a site of significant cholesterol synthesis, we determined the ileal distribution of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), the rate-limiting enzyme of the cholesterol biosynthetic pathway. Immunofluorescence microscopy on unfixed snap-frozen sections of ileum and jejunum from untreated rats or dogs showed HMG-CoA reductase in the absorpt...

BACKGROUND Recent studies have supported the hypothesis that calcific aortic stenosis is the product of an active inflammatory process, with similarities to atherosclerosis. We sought to determine whether therapy with hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) might slow the progression of aortic stenosis. METHODS AND RESULTS A retrospective study of 174 patients (mean ag...

We describe a method for estimating the total activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase (EC 1.1.1.34) in the small intestine of rats. An homogenate of the whole small intestine is prepared rapidly and assayed directly to maximize the yield of enzyme and to minimize opportunity for uncontrolled change in activity. Fresh homogenate inhibits the expression of reductase in hepa...

Running Title: Human HMG-CoA Lyase-Mg-Substrate/Inhibitor Structures To whom correspondence should be addressed: Jung-Ja P. Kim, Department of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226 Tel.: 414-955-8479 Fax: 414-456-6510, e-mail: [email protected]; Henry M. Miziorko, the Division of Molecular Biology and Biochemistry, University of Missouri-K...

We previously showed that human liver hydroxymethylglutaryl-CoA (HMG-CoA) lyase (HL; EC 4.1.3.4) is found in both mitochondria and peroxisomes. HL contains a 27-residue N-terminal mitochondrial targeting sequence which in cleaved on mitochondrial entry, as well as a C-terminal Cys-Lys-Leu peroxisomal targeting motif. Because peroxisomal HL has a greater molecular mass and more basic pI value th...

HMG-CoA reductase catalyzes the conversion of hydroxymethylglutarate to mevalonate, an important early rate-limiting step in the cholesterol biosynthesis pathway. Since the discovery of compactin, the first HMG-CoA reductase inhibitor, by Endo et al. in 1976, several other inhibitors have been described. Those that have been investigated in the clinic include mevastatin (compactin), lovastatin ...

Because the small bowel is a site of significant cholesterol synthesis, we determined the ileal distribution of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), the rate-limiting enzyme of the cholesterol biosynthetic pathway. Immunofluorescence microscopy on unfixed snap-frozen sections of ileum and jejunum from untreated rats or dogs showed HMG-CoA reductase in the absorpt...

THE FEEDBACK RESPONSE OF MEVALONATE: NADP oxidoreductase (acylating CoA; EC 1.1.1.34) in two varieties of hepatoma has been examined. In marked contrast to the feedback inhibition of this enzyme that is regularly observed in normal liver, the feedback control is completely lost in minimal-deviation hepatomas 9121 and 3924A. This finding provides the first specific biochemical localization of th...

Muscle problems and other adverse symptoms associated with statin use are frequent reasons for non-adherence and discontinuation of statin therapy, which results in inadequate control of hyperlipidemia and increased cardiovascular risk. However, most patients who experience adverse symptoms during statin use are able to tolerate at least some degree of statin therapy. Given the profound cardiov...